Whats the difference between voltage gated and ligand gated neurons?

Whats the difference between voltage gated and ligand gated neurons?

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How are they similar and how are they different?

There is no such thing as voltage gated or ligand gated NEURONS. I believe what you are refering to are what is known as voltage gated and ligand gated ion CHANNELS. Each neuron has both types of channels in their cell membrane.

Voltage gated ion channels open in response to voltage (i.e. when the cell gets depolarized) where as ligand gated channels open in response to a ligand (some chemical signal) binding to them.

Both types of channels are critical for proper activation of the post synaptic neuron. The pre synaptic neuron releases neurotransmitters into the synaptic cleft, these neurotransmitters then bind to the ligand gated channels, thus activating them. The ligand gated channels open up and allow the influx of sodium, which depolarizes the cell. This depolarization activates nearby voltage gated ion channels, which open up and let in even more sodium. Voltage gated sodium channels open up one region at a time, the previous region providing enough depolarization to activate the next regions voltage gated channels. This effectively allows the action potential to propagate through the cell.

4.3: How Neurons Communicate

  • Contributed by OpenStax
  • General Biology at OpenStax CNX
  • Describe the basis of the resting membrane potential
  • Explain the stages of an action potential and how action potentials are propagated
  • Explain the similarities and differences between chemical and electrical synapses
  • Describe long-term potentiation and long-term depression

All functions performed by the nervous system&mdashfrom a simple motor reflex to more advanced functions like making a memory or a decision&mdashrequire neurons to communicate with one another. While humans use words and body language to communicate, neurons use electrical and chemical signals. Just like a person in a committee, one neuron usually receives and synthesizes messages from multiple other neurons before &ldquomaking the decision&rdquo to send the message on to other neurons.

Exam 3 Study Guide (Mastering A&P)

What part of the nervous system performs information processing and integration?

A. central nervous system
B. somatic nervous system
C. parasympathetic nervous system
D. sympathetic nervous system

Which of the following is NOT a difference between graded potentials and action potentials?

A. Spatial summation is used to increase the amplitude of a graded potential temporal summation is used to increase the amplitude of an action potential.
B. Graded potentials can result from the opening of chemically gated channels action potentials require the opening of voltage-gated channels.
C. Greater stimulus intensity results in larger graded potentials, but not larger action potentials.
D. Graded potentials occur along dendrites, whereas action potentials occur along axons.

Which of the following is a factor that determines the rate of impulse propagation, or conduction velocity, along an axon?

A. degree of myelination of the axon
B. length of the axon
C. the number of axon collaterals extending from a truncated axon
D. whether the axon is located in the central nervous system or in the peripheral nervous system

At which point of the illustrated action potential are the most gated Na+ channels open?

What type of stimulus is required for an action potential to be generated?

A. hyperpolarization
B. a threshold level depolarization
C. a suprathreshold stimulus
D. multiple stimuli

How is an action potential propagated along an axon?

A. Stimuli from the graded (local) potentials from the soma and dendrites depolarize the entire axon.
B. An influx of sodium ions from the current action potential depolarizes the adjacent area.
C. An efflux of potassium from the current action potential depolarizes the adjacent area.

Why does the action potential only move away from the cell body?

A. The areas that have had the action potential are refractory to a new action potential.
B. The flow of the sodium ions only goes in one direction&mdashaway from the cell body

The velocity of the action potential is fastest in which of the following axons?

A. a small unmyelinated axon
B. a small myelinated axon
C. a large unmyelinated axon

Which of the following statements most accurately describes the effects caused by binding of the ligand shown to the structure labeled C?

A. The ligand is transported into the postsynaptic neuron.
B. The ligand is transported into the presynaptic neuron.
C. The membrane potential of the presynaptic membrane changes.
D. The membrane potential of the postsynaptic membrane changes.

Which pattern of neural processing works in a predictable, all-or-nothing manner, where reflexes are rapid and automatic responses
to stimuli in which a particular stimulus always causes the same response?

A. oscillative processing
B. parallel processing
C. serial processing
D. reflexive processing

Which of the following areas of the brain is responsible for spatial discrimination?

A. primary somatosensory cortex
B. vestibular cortex
C. Broca's area
D. gustatory cortex

Which of the following areas of the brain controls voluntary movement of the eyes?

A. gustatory cortex
B. frontal eye field
C. visual association area
D. primary visual cortex

Which of the following is NOT a function of the hypothalamus?

A. emotional responses
B. regulation of food intake
C. secretion of the hormone melatonin
D. regulation of body temperature

Which parts of the brain constitute the "emotional brain" known as the limbic system?

A. diencephalic and mesencephalic structures
B. cerebral and brain stem structures
C. cerebral and diencephalic structures
D. diencephalic and brain stem structures

Which part of the brain is considered the "gateway" to the cerebral cortex?

A. pons
B. hypothalamus
C. mesencephalon
D. thalamus

Prevents muscle overstretching and maintains muscle tone.

A. Stretch
B. Plantar
C. Crossed-extensor
D. Flexor
E. Tendon

Tests both upper and lower motor pathways. The sole of the foot is stimulated with a dull instrument.

A. Crossed-extensor
B. Stretch
C. Flexor
D. Plantar
E. Tendon

roduces a rapid withdrawal of the body part from a painful stimulus ipsilateral.

A. Stretch
B. Plantar
C. Flexor
D. Tendon
E. Crossed-extensor

Consists of an ipsilateral withdrawal reflex and a contralateral extensor reflex important in maintaining balance.

A. Flexor
B. Stretch
C. Crossed-extensor
D. Plantar
E. Tendon

Produces muscle relaxation and lengthening in response to tension the contracting muscle
relaxes as its antagonist is activated.

A. Plantar
B. Crossed-extensor
C. Stretch
D. Tendon
E. Flexor

The secretions of the adrenal medulla act to supplement the effects of ________.

A. parasympathetic innervation
B. vagus nerve activity
C. neurosecretory substances
D. sympathetic stimulation

The parasympathetic ganglion that serves the eye is the ________.

A. ciliary ganglion
B. submandibular ganglion
C. otic ganglion
D. pterygopalatine ganglion

Cardiovascular effects of the sympathetic division include all except ________.

A. dilation of the vessels serving the skeletal muscles
B. constriction of most blood vessels
C. increase of heart rate and force
D. dilation of the blood vessels serving the skin and digestive viscera

Sympathetic nerves may leave the spinal cord at which vertebra?

A. first coccyx
B. second cervical
C. first thoracic
D. third lumbar

The parasympathetic fibers of the ________ nerves innervate smooth muscles of the eye that cause the lenses to bulge to accommodate close vision.

A. abducens
B. oculomotor
C. trochlear
D. optic

Visceral reflex arcs differ from somatic in that ________.

A. visceral arcs contain two sensory neurons
B. somatic arcs contain one additional component that visceral arcs do not possess
C. visceral arcs involve two motor neurons
D. visceral arcs do not use integration centers

Once a sympathetic preganglionic axon reaches a trunk ganglion, it can do all but which one of the following?

A. pass through the trunk ganglion without synapsing with another neuron
B. synapse with a parasympathetic neuron in the same trunk ganglion
C. ascend or descend the trunk to synapse in another trunk ganglion
D. synapase with a ganglionic neuron in the same trunk ganglion

Sympathetic division stimulation causes ________.

A. increased blood glucose, decreased GI peristalsis, and increased heart rate and blood pressure
B. decreased blood glucose, increased GI peristalsis, and increased heart rate and blood pressure
C. increased blood glucose, increased GI peristalsis, and decreased heart rate and blood pressure
D. decreased blood glucose, increased GI peristalsis, and decreased heart rate and blood pressure

The route of major parasympathetic outflow from the head is via the ________.

A. vagus nerve
B. phrenic nerve
C. sympathetic trunk
D. sacral nerve

Where would you NOT find a cholinergic nicotinic receptor?

A. all parasympathetic target organs
B. all postganglionic neurons
C. skeletal muscle motor end plates
D. adrenal medulla hormone producing cells

Control of temperature, endocrine activity, and thirst are functions associated with the ________.

A. cerebellum
B. thalamus
C. hypothalamus
D. medulla

The parasympathetic tone ________.

A. causes blood pressure to rise
B. accelerates activity of the digestive tract
C. prevents unnecessary heart deceleration
D. determines normal activity of the urinary tract

Which of the following appears to exert the most direct influence over autonomic function?

A. medulla oblongata
B. hypothalamus
C. reticular formation
D. midbrain

Which is a uniquely sympathetic function?

A. regulation of body temperature
B. regulation of pupil size
C. regulation of respiratory rate
D. regulation of cardiac rate

Which of the following adrenergic neurotransmitter receptors plays the major role in heart activity?

Designing and Testing Neuromorphic Chips

This page describes how we design and test neuromorphic chips, starting with analysis of neurobiological data, then development of a neuron model, followed by layout of a multi-neuron chip for fabrication, and finally chip testing. Whether modeling axon migration, cochlear filtering, or thalamic nuclei, careful interpretation of neurobiological data is imperative. In each of these cases, the data is acquired using different experimental techniques—time-lapsed flourescence microscopy, laser interferometry, or the patch clamp—each with its own idiosyncrasies. It is important to interpret the fine details of individual experiments carefully, weighing both supporting and contradictory evidence, which seem to exist for every assertion made in biology. We develop this skill via neuroscience coursework, rotations in neurobiology labs, and critical reading of the literature.

How Neurons Work

The electrical characteristics of neurons are attributed to diffusion of various ions across the capacitive cell membrane via selective protein pores. These ion channels come in a wide variety and are highly selective for particular ions species (up to one in a million), with conductivity modulated by aspects of the local environment such as membrane voltage, ligand concentration, or enzymatic alteration. Various pumps set up gradients of specific ions across the membrane that ultimately create a negative resting membrane voltage of approximately &ndash70mV (relative to the extracellular fluid) for most neurons.

A neuron's electrical behavior influences that of other neurons through the action of ligand-gated ion-channels. The ligand, or neurotransmitter, is released at a synapse, the junction formed between one neuron's output wire, or axon, and another's input wire, or dendrite. As a result, particular ions flow into or out of the post-synaptic (receiving) neuron, causing its membrane voltage to depolarize (move closer to 0mV) or hyperpolarize (become more negative).

When synaptic currents bring a neuron's membrane voltage above the threshold necessary for activation of voltage-sensitive sodium channels, it discharges a voltage pulse. The upswing occurs as sodium ions flow into the cell, depolarizing it further. This positive feedback drives the voltage all the way to the rail. The downswing occurs as sodium channels inactivate and slower but more conductive (in the opposite direction) potassium channels activate. The entire pulse, called an action potential, transpires in less than a millisecond.

Action potentials travel down the neuron's axon, trigger neurotransmitter release at its terminals, thereby delivering synaptic inputs to target neurons, which in turn generate more action potentials.

Modeling Neurons with Transistors

Analytic models describing the behavior of ion-channels and their electrical effects on the neuron have been proposed since the mid 1900&rsquos. A predominant data source for these models is the patch-clamp, which measures both I-V (current-voltage) relationships and changes in channel currents or membrane voltage over time. In modeling neurons in our lab, we carefully evaluate contributions of various channels to the neuron&rsquos membrane voltage, and how best to capture their behavior using transistors and capacitors.

A neuron&rsquos function may be summarized in two steps: One, integration of synaptic inputs leading to membrane depolarization. Two, initiation of an action potential that propagates to the neuron&rsquos axon terminals. Such neuron models are called integrate-and-fire models. This is the simplest model employed, whether in software or in hardware. In this section, we describe the circuit-level design and analysis of a silicon-based integrate-and-fire neuron.

The six-transistor circuit shown above embodies the primary characteristics of our silicon neuron models. It is a leaky integrate-and-fire neuron, a stripped-down version of what we use in the lab. It consists of a membrane capacitance (center) to which input current is suppied (Iin), a positive-feedback loop to deliver sodium current to the membrane voltage (Ina), and a leak current to return the membrane to its resting potential upon reset.

The transistors in this circuit operate in the sub-threshold regime, where the channel current depends exponentially on the terminal voltages. The terminals and the direction of current flow are defined in the picture below notice that the pMOS gate has a circle (left) while the nMOS gate does not (right). For an nMOS transistor, the source voltage (Vs) is low (frequently zero, or ground). As the gate voltage (Vg) increases (from zero), the current flowing from the drain to the source increases exponentially. pMOS transistors have the opposite polarity: Vs is generally high (frequently at Vdd, the highest voltage on the chip), and as Vg decreases (from Vdd), the current increases exponentially.

Mathematically, the current–voltage relationships for pMOS and nMOS transistors are described by:
Ids = (w/l) * I0 * exp[(kVg - Vs)/uT)] for the pMOS
Isd = (w/l) * I0 * exp[-(kVg - Vs)/uT)] for the nMOS
where w and l are the channel's width and length, respectively I0 is the off current and uT is the thermal voltage (25mV at room temperature). These equations only apply when difference in voltage between source and drain exceeds 100mV, a condition known as saturation.

We will assume that the neuron is initially at rest. This means the membrane voltage (Vmem) is zero (ground) and the input voltage (Vinput) is zero, and hence the input current (Iin) is zero. In this state, the output voltage (Vout) is high (at Vref). This is a result of Vmem being zero, which cuts off the bottom right nMOS transistor and shorts the pMOS transistor directly above it, thereby isolating Vout from ground while tying it to Vref.

To excite the neuron, the voltage (Vinput) is increased from zero to a few hundred millivolts, causing Iin to turn on and charge the membrane capacitor, thereby increasing Vmem. As Vmem increases, the bottom right nMOS begins to conduct while the pMOS above it is still conductive (allbeit less so than it was before). Thus a path is created for current to flow into the current mirror (the two pMOS transistors labeled as such), which mirrors this current onto the membrane capacitor (Ina). Thus Vmem increases further, replicating the sodium channel's regenerative action.

Above are simulation results obtained for this simple neuron, displaying the behavior described. The input and sodium currents are shown (top, magenta and green respectively) the constant input current is so small (picoAmps) that it appears as zero on this microAmp scale. The membrane and output voltages are shown (bottom, magenta and green, respectively) one observes a slow and steady increase of membrane voltage as the input current integrates on the membrane capacitor. Threshold is reached around 3 microseconds Ina spikes causing a sharp increase in the membrane voltage.

This concludes the brief description of how we model an integrate-and-fire neuron using transistors and a capacitor. In the past, this component was generally unique for each chip designed, as different channel populations are used to model different neural processes and types. Now that we have developed a circuit that is versatile enough to model a wide variety of ion-channel types, that is no longer the case. A single neuron by itself, though, is insufficient to study population dynamics in neural circuits. This is where the beauty of VLSI comes into play. A neuron circuit is converted into an array of silicon neurons through the layout step described below.

Laying Out the Circuit

Once a circuit has been designed and simulated, the circuit must be layed out before it can be fabricated. Layout refers to drawing the layers that will be fabricated using a layout editor, a drawing program with integrated-circuit specific features (we use L-Edit by Tanner Tools).

We show the layout of two transistors (one nMOS and one pMOS) and a capacitor in the figure below their terminals are labeled. Gate is red and drain/source is green their intersection (the channel) is yellow. The brown and blue rectangles specify the doping of drain/source regions, thereby defining n- and p-type transistors, respectively. The green stipple pattern specifies a lightly doped n-region, called the well, within which the pMOS transistor (top-left) sits. The rest of the silicon area, called the substrate, is lightly p-doped, by default. Finally, the cyan regions are metal contacts made to the terminals.

The capacitor (right) is a transistor with one drain/source terminal missing and a large gate. The additional n-doped region abutting the one source/drain region creates an ohmic contact to the well (green stipple pattern). Similarly, the nMOS transistor could use a p-doped region to create a substrate contact.

We show the layout of integrate-and-fire neuron below. Metal wires are blue. Several nodes of the circuit are labeled: Vmem, Vdd, Gnd, Vinput, and Vleak. This is an atypically simple layout. Most layouts are considerably more complicated.

Time and effort must be devoted to lay out each transistor, capacitor, and wire carefully in order to strike the right balance between density and precision. Transistors must be sized to combat stochastic fluctuations in dopants (mismatch) and leakage currents. Larger transistors have both less mismatch and less leakage, but they take up much more area, limiting the number of neurons that can be fabricated on a single chip. On the other hand, the more tightly transistors are squeezed together, the more difficult it is to wire them together. Also, as circuits become more compact, close proximity to digital circuits couples noise into analog circuits.

After the neuron circuitry is layed out, it is tiled in an array and interfaced with peripheral asynchronous digital circuitry, which implements a standard communication protocol for communicating action potentials (or spikes). This is done with ChipGen, code developed in-house over the past several years. Layout for the entire chip is then verified against the schematic and checked for design-rule violations. Finally, the mask layers are exported and emailed to the fabrication service. We use MOSIS, a silicon broker that enables educational and commercial projects to be fabricated on shared runs at state-of-the-art fabs such as TSMC.

Testing the Chip

Once the chip has been fabricated and delivered, the real fun begins! Testing is a step-by-step process that begins at the circuit-level and ends (does it ever end?) at the system-level. The fabrication process is far from perfect and no two copies of a circuit are identical—even though they use the same layout. Transistor mismatch, leakage currents, and parasitic elements (e.g., capacitances) can wreak havoc on a poor design. In addition, simulations fail to account for noise introduced into the analog circuitry from proximal digital circuitry. Though some of these problems can be reduced with careful layout (as described above), the need for a robust analog design is obvious.

Chip testing is performed with the aid of a custom-designed printed circuit board (PCB). Properly designed, the PCB makes testing the chip a breeze. Improperly designed, life can become a nightmare of solder and wires. Unfortunately, learning the difference between the two sometimes requires hours of painful experience novices often don't get it right on the first attempt. Other than the chip itself, the board is populated with potentiometers, connectors, voltage regulators, test pins (many of them!) and additional onboard circuitry. Test pins are (obviously) a necessity for recording both digital and analog signals within the chip. Analog signals are monitored and recorded using an oscilliscope. Digital data can be captured using either a logic analyzer or a computer (via USB).

The initial testing phase determines how well the simulated model has survived fabrication. How do fabrication parameters vary across the chip? How have leakage currents affected the function of the circuit? At what bias levels does the chip perform optimally? This phase is simplified with a little foresight during layout. Running various voltage or current signals outside of the array (by including a scanner on the chip) helps in seeing how the various components in the model behave. Their function can then be compared to earlier extensive simulations. Otherwise, one is left with trying to figure out what is going on by looking at the output spikes.

Since we are modeling biology, we expect our chip to work like biology. Thus, the experimental procedure we use is very similar to that seen in the literature. For the retina, this may involve flashing patterns of light. For the cochlea, this may involve using various frequencies of sound. For a neuron model, this may involve repeating voltage clamp experiments. It is important for us to show that the components of our system replicate their biological analogs. Otherwise, we will have a difficult time convincing others that our artificial brain is working like the human brain.


Animals, cell culture, transfection, and plasmids

The use and care of animals were approved and directed by the Institutional Animal Care and Use Committee of Peking University and the Association for Assessment and Accreditation of Laboratory Animal Care. TRPV1-KO mice were provided by Z. Zhu (Third Military Medical University, Chongqing, China). Dyn1-KO mice were gifted by P. De Camilli (Yale University, New Haven, CT). Sprague-Dawley rats (

7 days old) were euthanized by an intraperitoneal injection of 0.15 ml of 10% chloral hydrate, and hypothermic anesthesia was used for mice. The DRGs of all spinal segments were isolated in ice-cold L15 medium (Gibco) and enzymatically dissociated in trypsin (0.2 mg/ml) and collagenase type 1A (1 mg/ml) containing Dulbecco’s modified Eagle’s medium/F12 for 40 min at 37°C. Cells were then dissociated by trituration and transfected with 3 μg of an NPY-pHluorin–expressing plasmid using a Neon (100-μl system) electroporation system (Invitrogen, MPK10096) according to the manufacturer’s instructions. The transfected cells were plated on polyethyleneimine-coated coverslips and cultured for 18 to 28 hours in a humidified incubator (37°C, 5% CO2) in Neurobasal-A medium supplemented with 2% B27 and 0.5 mM GlutaMAX-I (all from Gibco). NPY-pHluorin plasmid was constructed from NPY-Venus (a gift from N. Gamper, University of Leeds) and synapto-pHluorin (a gift from G. Miesenböck, University of Oxford). All chemicals were from Sigma, unless otherwise indicated.


DRG neurons transfected with NPY-pHluorin were fixed in 4% paraformaldehyde in phosphate-buffered saline (PBS) for 15 min at room temperature and permeabilized with 0.3% Triton X-100 for 5 min. Cells were blocked with 2% bovine serum albumin (BSA) in PBS for 1 hour at room temperature and then incubated overnight with primary antibodies diluted in PBS with 2% BSA at 4°C. After washing out the primary antibodies with blocking buffer, cells were incubated with Alexa Fluor 594–conjugated goat anti-rabbit immunoglobulin G (H+L) (Invitrogen, A11037) diluted in PBS with 2% BSA for 1 hour at room temperature. The nuclei were then stained with DAPI (4′,6-diamidino-2-phenylindole) and mounted with DAKO. Antibodies against CGRP (Peninsula, IHC6006) and secretogranin II (Abcam, ab12241) were used. Images were captured on an LSM 710 inverted confocal microscope (Carl Zeiss). For colocalization analysis, all intracellular puncta within 1-μm optical sections were selected and analyzed using the JACoP plugin of McMaster Biophotonics Facility ImageJ software (National Institutes of Health).

TIRF imaging, stimulation, and analysis

TIRF imaging was performed on an inverted microscope with a 100× TIRF objective lens (numerical aperture, 1.45 Olympus IX-81). Images were captured by an Andor electron-multiplying charge-coupled device using Andor iQ software with an exposure time of 50 ms. The standard bath solution contained the following: 150 mM NaCl, 5 mM KCl, 2.5 mM CaCl2, 1 mM MgCl2, 10 mM H-Hepes, and 10 mM d -glucose (pH 7.4). The temperature was kept at

35°C throughout all TIRF experiments using a laboratory-made heater. Exocytotic events were defined as abrupt fluorescence increases, immediately followed by a fluorescence decrease or diffusion of NPY-pHluorin puncta in the vicinity. For the analysis of single release events, each event was selected and marked with 1.92-μm-diameter (center) and 2.4-μm-diameter (annulus) circular areas. Fluorescence intensity was calculated and analyzed using ImageJ the intensity values during the 0.5-s baseline before the peak value were averaged and used as F0. In FFL (or spreading) events, a robust fluorescence increase occurred at both the center and the annular area of NPY-pHluorin puncta, representing the release and spread of NPY-pHluorin. KAR events showed a brief brightening of the puncta, but no or only a very limited fluorescence increase in the annular area, representing a transient opening and reclosure of a restricted fusion pore that limited the release of NPY. High K + [85 mM NaCl, 70 mM KCl, 2.5 mM CaCl2, 1 mM MgCl2, 10 mM H-Hepes, and 10 mM d -glucose (pH 7.4)] and capsaicin (300 nM) were applied using a gravity-fed perfusion system. Electrical field stimulation (1 ms, 15 V) was applied through a pair of platinum wires using an electronic stimulator (Nihon Kohden, SEN-3201) the negative pole was placed in the vicinity of the cell under examination. For two-color TIRF imaging, the Ca 2+ channels were labeled with mCherry (Cav2.2-mCherry and TRPV1-mCherry), and fusion events were visualized by NPY-pHluorin.

Fluorescence and fractional Ca 2+ measurements

Intracellular calcium ([Ca 2+ ]i) was measured using a Ca 2+ imaging system (TILL Photonics). Fura-2 potassium salt (1.0 mM) was loaded into the cell via a patch pipette in the whole-cell configuration. The fluorescence was sampled at 2 or 10 Hz.

Fractional Ca 2+ current, Pf, is defined as the percentage of Ca 2+ current in the total current passing through a cation channel (Im in this case). According to the original definition (40), P f = ∫ I Ca d t ∫ I m d t = Δ Fd F max × ∫ I m d t (1) where Im is the total whole-cell current and ICa is the proposed fractional Im current carried by Ca 2+ . ΔFd is the change of Fd, which is the “modified Ca 2+ -sensitive fura-2 signal” before (Fdt0) and after (Fdt1) the voltage pulse or ligand-induced Ca 2+ influx. Fd = F340 − F380, ΔFd = Fdt1 − Fdt0, and Fmax is a constant, which was determined by measuring the Ca 2+ influx through VGCCs in the solutions specified above. Under physiological conditions, all ions contributing to the current through VGCCs are Ca 2+ , namely, Pf = 100%. From Eq. 1, Fmax = ΔFd/∫ICadt, where ICa = Im (which is the current through VGCCs). According to Eq. 1, after determining the Fmax by measuring the fura-2 signal that is evoked after activation of TRPV1, the Pf of each channel can be determined.

CGRP immunoassay

Basal and stimulated extracellular CGRP concentrations were evaluated in freshly isolated DRG neurons using an enzyme immunometric assay kit (Bachem), following the manufacturer’s instructions. Cells were washed three times with normal external solution and then incubated in the same solution for 30 s at room temperature, followed by another 30-s incubation in this solution containing 70 mM KCl or 300 nM capsaicin. The incubation solutions were collected for subsequent analysis of basal and stimulation-coupled CGRP levels. All samples were centrifuged at 13,000 rpm for 5 min, and the supernatants were processed for CGRP measurement. Samples were analyzed at 450 nm using a microplate reader (BioTek Synergy 4). CGRP concentrations (in picograms per milliliter) were extrapolated from a best-fit line calculated from serial dilutions of a CGRP standard. All data points were measured in triplicate.

Electrophysiological recordings

We used an EPC10/2 amplifier with Pulse software (HEKA Elektronik) to obtain whole-cell patch-clamp recordings as described previously (41, 42). Pipette resistance was controlled between 3 and 4 megohms when filled with an internal solution containing 153 mM CsCl, 1 mM MgCl2, 10 mM Hepes, and 4 mM Mg–adenosine 5′-triphosphate (pH 7.2). Normal external solution contained 150 mM NaCl, 5 mM KCl, 2.5 mM CaCl2, 1 mM MgCl2, 10 mM Hepes, and 10 mM glucose (pH 7.4). Igor software (WaveMetrics) was used for all offline data analyses. All experiments were performed at room temperature, unless otherwise indicated.

Calcium imaging

Changes of the [Ca 2+ ]i in DRG neurons were measured as the Fluo-4/Fura-Red fluorescence ratio (43). Cells were loaded with 2.5 μM Fluo-4 AM and 5 μM Fura-Red AM (Invitrogen) dissolved in 0.2% dimethyl sulfoxide and 0.04% Pluronic F-127 in a standard bath solution at 37°C for 20 min. Cells were then washed and imaged on an inverted confocal microscope (Zeiss LSM 710). The fluorescent Ca 2+ indicators were excited using a 488-nm laser, and the light emitted from the Fluo-4 and Fura-Red was recorded on separate channels at 500 to 540 nm and 600 to 680 nm, respectively. Images (512 × 512 pixels) were acquired at 1 Hz under a 40× oil objective lens (Zeiss). The Ca 2+ level was determined from ROIs using the ratio of intensity traces recorded on the Fluo-4 and Fura-Red channels.


All experiments were replicated at least three times. Data were analyzed offline using ImageJ and Igor software. Data are means ± SEM. Statistical comparisons were performed using two-tailed unpaired Student’s t test, Kolmogorov-Smirnov test, or Mann-Whitney U test, as indicated. All tests were conducted using SPSS 13.0 (Statistical Package for the Social Sciences). Significance threshold was set at P < 0.05.


Central Nervous System: Brain and spinal cord. Spinal fluid goes through the ventricles. No nerve endings Peripheral Nervous System: Senses coming into the central nervous system OR motor system (heart, breathing) Somatic Motor System - skeletal muscles Internal (tummy aches) and external (touching and feeling) environment

Nerve Cell Morphologies Cell Body: “Where the action happens” RNA, DNA. Dendrites: Information goes out, information is received Axon: Info comes in, sends it out -&gt both coming off either side of the cell body

-&gt Neuron: Function: - Inter-cellular communication: the transfer of information from one cell to another - Electrical signalling Convergence: Number of inputs to one neuron. Multiple neurons -&gt one neuron Divergence: Number of targets. One neuron -&gt multiple neurons Interneurons: Short. Transfer information to each other Submillimeter in length Projection: Longer. Can be meters

Types of Neuronal Electrical Signalling Resting Membrane Potential: Always negative (-40 to -90mV) A negative potential generated by neurons that can be measured by recording voltage between the inside and outside of nerve cells Receptor Potential: Activation by external stimulus - Usually by touch, can be heat - High and low frequency touch

  • Harder touch = higher potential
  • Synaptic Potentials:* Transmission from one neuron to another. Serve as the means of exchanging information in the complex of neural circuits found in both the central and peripheral nervous systems Synaptic potentials are the incoming signals to the neuron. When the neuron is depolarised to threshold, it generates an action potential. The action potential is the outgoing signal of the neuron
  • Action Potential:* Travels along axon (spikes). Always exactly the same and has a threshold Special type of electrical signal that travels along their axons. Responsible for long-range transmission of information within the nervous system and allow the transmission of information to its target organs Generated by the neuron and typically is a brief change from negative to positive in the transmembrane potential These are considered ‘active responses’ because they are generated by selective changes in the permeability of the neuronal membrane

Currents - Neutral state of an atom - Like charges repel, unlike charges attract -&gt cells are the same to generate electrical currents

Recording Electrical Signals in Nerve Cells - Two electrodes inserted into a neuron - one injects current and the other records Hyperpolarization: Becoming more negative Depolarisation: Becoming less negative. Depolarise neurons until they reach threshold Passive Response: When a cell does not reach its action potential whilst being hyper/depolarised Action Potential: Active response/amplitude is independent of input

Passive Current - Progressive decrease over distance - Current leaks out across membrane Active Current - Action potential boost current - Electrical current sustained over long distances - Movement of ions across membrane - Called active because it generates its own electrical current Electrical Potential - Differences in concentration of ions across membrane - Membranes are selectively permeable to different ions based on which “gates” are open

Myelinated Axons - Cells made up of fat that wraps around the axon, insulating it to stop the current bleeding out - No channels where myelination is Nodes of Ranvier: Gaps in the myelinated axon containing channels - Action potentials diffuse along due to insulation, called saltatory action potential. Much quicker than axons without myelination - Thicker axons = Further gaps = Much quicker - Involves active and passive currents


    1. The patellar tendon is hit with the reflex hammer.
    2. Sensory stretch receptors in the muscle fiber sends sensory information to the spinal cord.
    3. That sensory information enters the spinal cord via the dorsal root and synapses on an interneuron and a motor neuron in the ventral horn.

      • The motor neuron then sends motor information away from the spinal cord via the ventral root.
      • The motor neuron send a signal to the quadriceps muscle fiber to contract.
      • The interneuron prevents a separate motor neuron from allowing the hamstring to contract.

      Title: Patellar Reflex Arc | Author: Backyard Brains | License: CC BY-SA 3.0

      Chapter 12 Nervous Tissue

      Make certain that you can define, and use in context, each of the terms listed below, and that you understand the significance of each of the concepts.

      1. Identify the major structures and functions of the nervous system in the maintenance of homeostasis.
        1. nervous system
          1. organization of the nervous system
          2. central nervous system (CNS)
            1. brain
            2. spinal cord
            1. sympathetic
            2. parasympathetic
            1. sensory function
            2. integrative function
            3. motor function
              1. effector
              1. histology
                1. electrical excitability
                2. action potentials (or nerve impulses)
                3. parts of a neuron
                  1. cell body
                  2. Nissl bodies
                  3. dendrite
                  4. axon
                  5. axon hillock
                  6. initial segment
                  7. trigger zone
                  8. axon collateral
                  9. axon terminal
                  10. synapse
                  11. synaptic end bulb
                  12. varicosities
                  13. synaptic vesicle
                  14. neurotransmitter
                  15. fast axonal transport
                  16. slow axonal transport
                  1. sensory
                  2. motor
                  3. interneurons
                  1. neuroglia or glia
                  2. astrocytes
                  3. oligodendrocytes
                    1. myelin sheath
                    2. myelinated
                    1. myelinated and unmyelinated
                    2. neurolemma
                    3. nodes of Ranvier
                    4. clusters of neuronal cell bodies&mdashnucleus
                    5. bundles of axons&mdashtracts
                    6. white matter
                    7. gray matter
                    1. graded potentials
                    2. action potentials
                      1. muscle action potential
                      2. nerve action potential
                      1. membrane potential
                      2. resting membrane potential
                      3. current
                      1. ion channel
                        1. electrochemical gradient
                        2. leak channel
                        3. ligand-gated ion channel
                        4. mechanically-gated ion channel
                        5. voltage-gated ion channel
                        1. resting membrane potential
                        2. polarized
                        3. factors that contribute to the resting membrane potential
                        4. graded potential
                          1. hyperpolarizing graded potential
                          2. depolarizing graded potential
                          3. decremental conduction
                          4. summation
                          1. action potential (AP) or impulse
                          2. threshold
                            1. subthreshold stimulus
                            2. threshold stimulus
                            3. suprathreshold stimulus
                            1. absolute refractory period
                            2. relative refractory period
                            1. nerve impulse propagation (or conduction)
                            2. continuous conduction
                            3. saltatory conduction
                            4. factors that affect the speed of propagation
                            5. classification of nerve fibers
                            6. encoding of stimulus intensity
                            7. comparison of electrical signals produced by excitable cells
                            1. synapse
                              1. presynaptic neuron
                              2. postsynaptic cell
                              3. postsynaptic neuron
                              4. effector cell
                              5. axodendritic
                              6. axoaxonic
                              7. electrical synapse
                              8. gap junctions
                              9. advantages
                              10. chemical synapse
                              11. synaptic cleft
                              12. postsynaptic potential
                              13. synaptic delay
                              14. transmission of signals at a chemical synapse&mdash7 steps
                              15. excitatory postsynaptic potential (EPSP)
                              16. inhibitory postsynaptic potential (IPSP)
                              17. neurotransmitter receptors
                              18. removal of neurotransmitter
                              1. summation
                                1. spatial summation
                                2. temporal summation
                                  1. EPSP
                                  2. nerve impulses
                                  3. IPSP
                                  1. neurosecretory cells
                                  2. neurotransmitters
                                    1. acetylcholine
                                      1. amino acids
                                      2. glutamate
                                      3. gamma-aminobutyric acid (GABA)
                                      4. glycine
                                      1. norepinephrine
                                      2. epinephrine
                                      3. dopamine
                                      4. catecholamines
                                      5. serotonin
                                      1. enkephalins
                                      2. endorphins
                                      1. neural circuits
                                        1. simple series
                                        2. diverging circuit
                                        3. converging circuit
                                        4. reverberating circuit
                                        5. parallel after discharge circuit
                                        1. neurogenesis in the CNS
                                          1. plasticity
                                          2. neurogenesis
                                          1. multiple sclerosis (MS)
                                          2. epilepsy

                                          Complete the &ldquoChapter Review and Resource Summary&rdquo at the end of the chapter.

                                          Work through the &ldquoCritical Thinking Questions&rdquo for this chapter in WileyPLUS and ORION.

                                          CH 105 - Chemistry and Society

                                          Neurobiochemistry is one of the most explosive areas of biological research. Scientists are now starting to unravel the molecular bases for memory, cognition, emotion, and behavior. The next decades will bring truly revolutionary understanding of brain chemistry and along with it the potential to alter human mood, memory, and to treat mental illness such as schizophrenia much more effectively. The human brain, with about 100 billion neurons (each which can form connections - synapses - with 1000 to 10,000 other neurons ) and associated glial cells (10-50 times the number of neurons) can be considered one of the most complex structures in the universe. This section will explore the biology and chemistry of neurons.

                                          THE RESTING POTENTIAL AND ACTION POTENTIALS

                                          Neurons consist of a single, nucleated cell body with multiple signal-receiving outgrowths (dendrites) and multiple-signal sending outgrowths (axons) which end in a terminal button. These interact through the synapse with dendrites on other neurons.

                                          A presynaptic neuron can stimulate an adjacent postsynaptic neuron by releasing a neurotransmitter into the synapse between the cells, which binds to a receptor in the membrane of the post-synapatic cell, stimulating the cell. We will discuss the events which cause the post-synaptic cell to "fire", but we will not discuss the immediate events which lead to the release of neurotransmitter by the presynaptic neuron.

                                          Neurons (as do all cells) have a transmembrane voltage difference or potential across the membrane. Transient changes in the membrane potential are associated with neuron activation or inhibition. This arises in part due to the imbalance of sodium and potassium ions across the membrane which were established by a protein , Na + -K + -ATPase, in the membrane. This protein transfers 3 Na + ions out of the cytoplasm for every 2 K + ions it transports in, which generates a transmembrane potential. Likewise Cl - has a much higher level outside the cell. Membrane potentials are determined not only by the size of the ion gradients across the membrane, but also the differential permeability of membranes to ions. Synthetic bilayer membranes are not very permeable to ions. This should follow from your understanding of intermolecular forces: ions are not stabilized by nonpolar molecules and are not soluble in nonpolar solvents. the table below shows permeability of various ions to a liposome which is a bilayer without membrane proteins.

                                          Ion permeability of phosphatidyl serine vesicles

                                          ION PERMEABILITY (cm/s)
                                          sodium <1.6 x 10 -13 (lowest)
                                          potassium <9 x 10 -13
                                          chloride <1.5 x 10 -11 (highest)

                                          Now check out the table below which shows the concentrations of ions inside cells and outside (for example in the blood) and their permeabilities to mammalian bilalyer membranes.

                                          T ypical ion concentrations and permeabilities for mammalian membranes.

                                          Ion Cell (mM) Blood (mM) Permeability (cm/s)
                                          potassium 140 5 5 x 10 -7
                                          sodium 5-15 145 5 x10 -9
                                          chloride 4 110 1 x 10 -8
                                          X- (neg. macromol.) 138 9 0

                                          How can we account for the markedly greater permeabilities of ions (1000x to 1,000,000 x) in mammalian cell membranes compared to synthetic lipid vesicles? Glucose also has a greater permeability through red blood cell membranes than through synthetic liposomes because of a membrane receptor that allows facilitated diffusion across the membrane and down a concentration gradient.

                                          The same thing is true of ion permeabilites in intact biologicial membranes. These membranes have several types of selective ion channels (nongated - always open, and gated - open only after specific shape changes in the protein). The nongated channels dramatically increase the permeability of membranes to ions, as the glucose transport protein increased the permeabilty to glucose. Ion channels in nerve and muscle can move ions across the membrane at a rate up to 10 9 /s..

                                          The Transmembrane Potential

                                          How is the transmembrane potential formed? Both glial cells (which function as protectors, scavengers, and feeder for brain neurons) and neurons have transmembrane potentials. First consider glial cells.

                                          Glial Cells

                                          The transmembrane ion gradients for ions are established, in part, through the action of ion-specific ATPases, such as we discussed with the Na/K ATPase. This transporter ejects 3 sodium ions from the inside of the cell for every 2 potassium ions in transports in, all against a concentration gradient. This makes the inside more "negative" than the outside, which contributes to the transmembrane potential. But note also that there is a Cl ion gradient across the membrane also. If another transporter moves Cl - ions to the outside of the cell in equal amounts as for Na + ions, no charge imbalance would exists across the membrane and no transmembrane potential would exist. In addition, might not any initial charge imbalance across the membrane, which would lead to a transmembrane potential, collapse as the ion gradient collapses as sodium flow back across the membrane down its concentration gradient and potassium ions flow out?

                                          Two things must occur for a membrane potential to be formed and be stable.

                                          • First, there must be a concentration gradient of charged ions (for example, sodium, potassium, or chloride) across the membrane. This arises from proteins like the sodium/potassium ATPase.
                                          • Second, the membrane must be differentially permeable to different ions. Differential permeabilities arise from different transmembrane protein ion channels, like a Na channel, or K channel, in membrane

                                          With respect to ion channels, glial cells appear to have only a non-gated potassium channel, which allows the outward flow of potassium ions down the concentration gradient. The inside will then have a net negative charge since impermeable anions remain. Sodium can't get from the outside to the inside through a channel. The concentration gradient causes this outward flow of potassium ions. As more ions leave, the inside gets more negative, and a transmembrane potential which resists further efflux of potassium develops. Eventually they balance, and the net efflux of potassium stops. The resting transmembrane potential reaches -75 mV .

                                          We can easily measure the actual transmembrane potential of cells. Varying the outside sodium and potassium concentrations would change the experimental transmembrane potential,. The experimental resting potentials of glial cells always matched the theoretical potassium potentials, supporting the view that the transmembrane potential was associated only with open, nongated potasisum channels. This was not observed with neurons, suggesting that channels other than for potassium were open. It became clear that nerve cells were permeable not only to potassium, but also to sodium and chloride. How do these work in establishing the resting potential? Consider the simplest case when just potassium channels are present, along with an unequal distribution of other ions. Now add some sodium channels. Two forces act to drive sodium into the cell - the concentration gradient, since sodium is higher on the outside, and the membrane potential since the inside of the cell is negative. The equilibrium potential of a cell if it were only permeable to sodium is +55 mv, so there is a great electrical drive for sodium to enter through the nongated, open sodium pores we just added. As sodium enters, the cell starts to "depolarize" and have a more positive voltage. However, since in our example, there are many more open potassium channels, the resting potential deviates only a small amount from the potassium potential, since as the potential becomes more positive, more potassium flows out down the concentration gradient. Eventually the enhanced potassium efflux equals the sodium influx, and a new resting membrane potential of -60 mV is established, which is typical of neurons. In the resting cells, the passive fluxes of sodium and potassium ions are exactly balanced by the active fluxes of these ions mediated by the Na/K ATPase.

                                          BINDING OF NEUROTRASMITTER TO RECEPTORS: CELL ACTIVATION

                                          What happens when a neurotransmitter binds to a receptor on the post-synaptic cell?

                                          • Stimuli are received from hundreds to thousands of different neurons.
                                          • Nerves receive both excitatory and inhibitory stimuli from neurotransmitters
                                          • Different kinds of receptors are present to receive stimuli, which control the activity of different kinds of channels.
                                          • The ion channels in neurons are gated by a variety of mechanisms: changes in membrane potential, iheat, cold, stretch, or covalent modification.

                                          Now what happens when a neurotransmitter binds to the receptor on the post-synaptic cell? A depolarization occurs (mediated by conformational changes in the transmitter-receptor complex) raising the membrane potential from the initial steady level. What happens next depends on the identity of the post synaptic cell. In a neuron, the rising potential triggers an action potential by opening voltage-gated sodium channels. The potential rises to about + 35 mV, but does not reach the Na ion equilibrium potential, because the high positive potential opens a voltage-gated potassium channel. The potential then falls until it reaches the K ion equilibrium potential where the cells is hyperpolarized. It slowly then relaxes back to the resting potential of -60 mV. This wave of changes in potential sweeps down the post-synaptic cell membrane and is the basis for the "firing" of the neuron.

                                          The following incredible animations come from: Neurobiology by Gary Matthews.

                                          • Chemical Synapse
                                          • Membrane-Bound Receptors, G Proteins, and Ca2+ Channels
                                          • Voltage Gated Channels and the Action Potential
                                          • Sodium-Potassium Exchange
                                          • Function of the Neuromuscular Junction
                                          • Action Potential Propagation in an Unmyelinated Axon
                                          1. Na + -K + -ATPase: It transports both sodium and potassium ions against a concentration gradient using ATP as an energy source. Without this protein, the membrane potential could not be maintained since the sodium and potassium gradient would collapse. It also contributes to the potential. (In addition, we have seen that ungated potassium and sodium channels are also present.)
                                          2. Neurotransmitter receptor: The receptors we will consider here are typically neurotransmitter-gated ion channels. Once the neurotransmitter binds, a shape change occurs in the transmembrane receptor protein, allowing a flow of ions down a concentration gradient. Depending on the nature of the ion, the channel either initiates depolarization (when Na + enters from the outside and raises the transmembrane potential) or inhibits depolarization (when Cl - enters from the outside and lowers it. When chloride channels open, they hyperpolarize the transmembrane potential. Stimulatory neurotransmitters (like glutamate) lead to depolarization of the membrane, while inhibitory neurotransmitters (like gamma-aminobutyric acid or GABA) lead to hyperpolarization of the membrane (make the potential more negative). We will soon read that ethanol directly affects the GABA channel in neural membranes.
                                          3. Na + channel (voltage-gated): When the neurotransmitter-gated channel depolarizes the membrane to some threshold value, sodium channels undergo a shape change and open allowing Na + ions to flood into the cell, raising the potential to a positive approx. 33 mV. This membrane protein is a voltage-gated channel, not a neurotransmitter-gated one. Somehow, it senses a change in the transmembrane potential initiated by opening of the ligand-gated channel.
                                          4. K + channel (voltage gated): When the membrane potential reaches around +25 mV or so, the K + channel, a voltage-gated membrane protein, alters its conformation, allowing K + efflux from the cells, lowering the potential until it reaches the potassium equilibrium potential. It slowly relaxes back to the cell resting potential of about -60 mV.
                                          5. Cl - channel: If these channels (typically ligand-gated) are open, they will hyperpolarize the cell and make it more difficult to fire.

                                          Chime Molecule Modeling: Acetylcholine Receptor Pore | Jmol (1OED)

                                          Excitatory Neurotransmitters in the Brain:

                                          Glutamate is a major excitatory neurotransmitter in the brain. Four types of glutamate receptors are found in the central nervous system. They differ in the nature of neurotransmitter which bind to the receptor and which act as agonists. Excessive amounts of glutamate are neurotoxic.

                                          Inhibitory Neurotransmitters:

                                          The main inhibitory neurotransmitters are GABA (gamma-aminobutyric acid )and glycine. They bind to neurotransmitter-gated chloride channels, which when open hyperpolarize the membrane (make the transmembrane potential more negative) and hinder neuron firing. Benzodiazepines (like Valium and Librium - anti-anxiety and muscle-relaxing agents) and barbituates (like phenobarbital-hypnotics) bind at sites other than site where GABA binds and potentiate (increase) the binding of each other and GABA.

                                          • GABA Biochemistry
                                          • GABA Receptors
                                          • Benzodiazepines: agonists, antagonists and inverse agonists
                                          • Inverse Agonists: a reasonable explanation
                                          • GABA Channel Animation
                                          • Animation: alcohol/GABA
                                          • Summary Picture: GABA Channel Activity
                                          • Of Mice and Alcohol

                                          In summary, neurotransmitter and voltage gated channels allow changes in the polarization of the membrane. Other mechanisms can also lead to changes. Membrane proteins can be phosphorylated (using ATP) by protein kinases in the cell, leading to a change in the conformation of the membrane protein, and either an opening or closing of the channel. Channels linked to the cytoskeleton of the cells can also be opened or closed through stretching. Other stimuli that gate channels are light (through photoisomerization-induced conformational changes), heat, and cold.

                                          Neurotransmitters can act as signals to open ion-specific, ligand-gated membrane channels, which change the transmembrane potential. In other words, the neurotransmitters gate the channels directly. Typical examples of channels directly gated by neurotransmitters are the acetylcholine receptor in neuromuscular junctions and the Glu, Gly, and GABA receptors in the central nervous system. Receptors with direct gating of ion flow are fast, with activities that last milliseconds, and are used in eliciting behavioral responses.

                                          However, ion channels can also be gated indirectly when the neurotransmitter binds to its receptor and leads to events which open an ion channel that is distinct from the receptor. In this case, the occupied receptor communicates to an ion channel indirectly through activation of kinases which can phosphorylate other protein including other neurotransmitter receptors. Example of this indirect gating of ion channels include the serotonin, adrenergic, and dopamine receptors in the brain. These receptors, when they bind neurotransmitters, lead to the increase of second messenger levels (such as cAMP) in the neuron. This can either activate kinases in the cell, which phosphorylate ion channels to either open or close them, or can bind directly to the channel and modulate its activity through a direct shape change. In contrast to direct gating, receptors that indirectly gate ion channels have activities that are slow and last seconds to minutes. These receptors are usually involved in modulating behavior by changing the excitability of neurons and the strength of neural connections, hence modulating learning and memory.

                                          • Web Textbook on Nerve Impulses - with interactive simulations of ions channels (this is an awesome web site)
                                          • World's Neurochemistry Portal - from the International Society for Neurochemistry
                                          • I on channels for beginners.

                                          Alcohol and Drug Effects on Neurons

                                          You should now have enough background to read some recent scientific articles on the action of alcohol and other drugs on neurons. Please refer to the class schedule and WebCT for specific reading assignments. I will add additional summarizes below from recent studies if warranted.

                                          Alterations of potassium channel have recently been implicated in the inhibitory effects of ethanol. Davies, McIntire, et al. studied effects of ethanol on the round worm C. elegans, believing that alcohol-mediated inhibition of neural activity would be conserved across species. Previously it has been shown that the dose required for behavioral changes is similar for both invertebrates and vertebrates. Ethanol seems to affect many different proteins that would lead to synaptic inhibition, including GABA and glutamate channels and potassium channels. Many different gene products (dopamine D4 receptors, protein kinase C) are associated with increased sensitivity while others (nitric oxide synthase, dopamine D2) are associated with ethanol resistance. These changes suggests that complex pathways are involved in ethanol effects but they didn't isolate a specific target for its effects.

                                          When C. elegans were exposed to ethanol for brief time periods, ethanol levels rose to values similar to levels seen in intoxicated drivers (0.1%). They isolated mutants that were resistant to the inhibitory effect of ethanol (which in this organism were observed as changes in movement and egg-laying behavior). These mutants affected a single gene, slo-1, homologous to the the slowpoke gene in drosophila. The gene in both organisms encoded a potassium channel, whose normal function is to repolarize neural membranes to their resting potential. The normal channel is activated by ethanol, which enhances K + efflux, making the transmembrane potential more negative, which makes inhibits neural firing (the same outcome as when ethanol enhances Cl- influx through GABA channels). Mutants strains (resistant to alcohol), when transformed with slo-1+ regained ethanol sensitivity. Ethanol appears to directly activate the channel. This would lead to efflux of potassium ions from the worm, hyperpolarizing the neural cells, leading to inhibition of neural activity. Effects in C. elegans were observed at physiologically relevant ethanol, ranging from those that produce euphoria to sedation in humans.

                                          Davies, A. et al. A Central Role of the BK Potassium Channel in Behavioral Response to Ethanol in C. Elegans. Cell, 115, pg 655 (2003)

                                          Watch the video: Ion channels voltage gated, ligand gated, stress activated ion channel (November 2022).