User:WillowW/Action potential jetsam

Sundry facts under Stimulus phase

To provoke an action potential, the stimulus must depolarize the axon hillock sufficiently strongly, above a threshold that depends on the axon's recent activity.

above the voltage at which the inwards current of sodium ions outweighs the outwards current of potassium ions.  

A local membrane depolarization caused by an excitatory stimulus causes some voltage-gated sodium channels in the axon hillock membrane to open, causing net inward movement of sodium ions through the channels along their electrochemical gradient. This movement of sodium ions across the membrane is an example of facilitated diffusion. Because they are positively charged, the inward moving sodium ions make the potential difference across the membrane less negative inside. This initial inward movement of sodium ions is favored by both the negative-inside membrane potential and the concentration gradient of sodium ions across the membrane (less sodium inside). The movement of individual sodium ions involves many random molecular collisions and at any particular moment a sodium ion might be moving outward, but the net movement of sodium is inward, as determined by the electrochemical gradient.

A plot of current (ion flux) against voltage (transmembrane potential) illustrates the action potential threshold (red arrow) of an idealized cell.

Action potentials are triggered when an initial depolarization reaches the threshold. This threshold potential varies, but generally is about 15 millivolts more positive than the cell's resting membrane potential, occurring when the inward sodium current exceeds the outward potassium current. The net influx of positive charges carried by sodium ions depolarizes the membrane potential, leading to the further opening of voltage-gated sodium channels. These channels support greater inward current causing further depolarization, creating a positive-feedback cycle that drives the membrane potential to a very depolarized level.

The action potential threshold can be shifted by changing the balance between sodium and potassium currents. For example, if some of the sodium channels are in an inactivated state, then a given level of depolarization will open fewer sodium channels and a greater depolarization will be needed to trigger an action potential. This is the basis for the refractory period.

Action potentials are largely dictated by the interplay between sodium and potassium ions (although there are minor contributions from other ions such as calcium and chloride), and are often modeled using hypothetical cells containing only two transmembrane ion channels (a voltage-gated sodium channel and a non-voltage-gated potassium channel). The origin of the action potential threshold may be studied using I/V curves (right) that plot currents through ion channels against the cell's membrane potential. (Note that the illustrated I/V is an "instantaneous" current voltage relationship. It represents the peak current through channels at a given voltage before any inactivation has taken place (i.e. ~ 1 ms after stepping to that voltage) for the Na current. The most positive voltages in this plot are only attainable by the cell through artificial means: voltages imposed by the voltage-clamp apparatus).

Four significant points in the I/V curve are indicated by arrows in the figure:

1. The green arrow indicates the resting potential of the cell and also the value of the equilibrium potential for potassium (E_k). As the K⁺ channel is the only one open at these negative voltages, the cell will rest at E_k.
2. The yellow arrow indicates the equilibrium potential for Na⁺ (E_Na). In this two-ion system, E_Na is the natural limit of membrane potential beyond which a cell cannot pass. Current values illustrated in this graph that exceed E_Na are measured by artificially pushing the cell's voltage past its natural limit. Note however, that E_Na could only be reached if the potassium current were absent.
3. The blue arrow indicates the maximum voltage that the peak of the action potential can approach. This is the actual natural maximum membrane potential that this cell can reach. It cannot reach E_Na because of the counteracting influence of the potassium current.
4. The red arrow indicates the action potential threshold. This is where I_sum becomes net-inward. Note that this is a zero-current crossing, but with a negative slope. Any such "negative slope crossing" of the zero current level in an I/V plot is an unstable point. At any voltage negative to this crossing, the current is outward and so a cell will tend to return to its resting potential. At any voltage positive of this crossing, the current is inward and will tend to depolarize the cell. This depolarization leads to more inward current, thus the sodium current become regenerative. The point at which the green line reaches its most negative value is the point where all sodium channels are open. Depolarizations beyond that point thus decrease the sodium current as the driving force decreases as the membrane potential approaches E_Na.

The action potential threshold is often confused with the "threshold" of sodium channel opening. This is incorrect, because sodium channels have no threshold. Instead, they open in response to depolarization in a stochastic manner. Depolarization does not so much open the channel as increases the probability of it being open. Even at hyperpolarized potentials, a sodium channel will open very occasionally. In addition, the threshold of an action potential is not the voltage at which sodium current becomes significant; it is the point where it exceeds the potassium current.

Biologically in neurons, depolarization typically originates in the dendrites at synapses. In principle, however, an action potential may be initiated anywhere along a nerve fiber. In his discovery of "animal electricity," Luigi Galvani made a leg of a dead frog kick as in life by touching a sciatic nerve with his scalpel, to which he had inadvertently transferred a negative, static-electric charge, thus initiating an action potential.

Overview

An action potential is a depolarizing all-or-nothing stimulus that propagates along a cell's surface without losing intensity. There is always a difference in electrostatic potential between the inside and outside of a cell, i.e. the cell is polarized. This membrane potential is the result of the distribution of ions across the cell membrane and the selective permeability of the membrane to these ions. The voltage of an inactive cell remains close to a resting potential with excess negative charge inside the cell. When the membrane of an excitable cell becomes depolarized beyond a threshold, the cell undergoes an action potential (it "fires"), often called a "spike" (see Threshold and initiation).

The action potential results from the flow of ions through channels in the plasma membrane, and is not due to molecules or structures within the cytoplasm. This was demonstrated dramatically by squeezing out the cytoplasm of a squid axon, and replacing it with an equivalent ionic solution. The perfused axon can generate normal action potentials, indeed, hundreds of thousands of them over many hours. By changing the ionic concentrations within and without the perfused axon, the theoretical equations describing the action potential were verified. Moreover, the laws governing the flow of ions across the membrane are sufficient to reconstruct the form of the action potential.

An action potential is a rapid change of the polarity of the voltage from negative to positive and then vice versa, the entire cycle lasting on the order of milliseconds. Each cycle — and therefore each action potential — has a rising phase, a falling phase, and finally an undershoot (see Phases). In specialized muscle cells of the heart, such as cardiac pacemaker cells, a plateau phase of intermediate voltage may precede the falling phase, extending the action potential duration into hundreds of milliseconds.

The action potential does not dwell in one location of the cell's membrane, but travels along the membrane (see Propagation). It can travel along an axon for long distances, for example to carry signals from the spinal cord to the muscles of the foot. After traveling the whole length of the axon, the action potential reaches a synapse, where it stimulates the release of neurotransmitters. These neurotransmitters can immediately induce an action potential in the next neuron to propagate the signal, but the response is usually more complex.

Both the speed and complexity of action potentials vary between different types of cells, but their amplitudes tend to be roughly the same. Within any one cell, consecutive action potentials are typically indistinguishable. Neurons are thought to transmit information by generating sequences of action potentials called "spike trains". By varying both the rate as well as the precise timing of the action potentials they generate, neurons can change the information that they transmit.

Evolutionary advantage

The action potential, as a method of long-distance communication, fits a particular biological need seen most readily when considering the transmission of information along a nerve axon. To move a signal from one end of an axon to the other, nature must contend with physics similar to those that govern the movement of electrical signals along a wire. Due to the resistance and capacitance of a wire, signals tend to degrade as they travel along that wire over a distance. These properties, known collectively as cable properties set the physical limits over which signals can travel. Thus, nonspiking neurons (which carry signals without action potentials) tend to be small. Proper function of the body requires that signals be delivered from one end of an axon to the other without loss. An action potential does not so much propagate along an axon, as it is newly regenerated by the membrane voltage and current at each stretch of membrane along its path. In other words, the nerve membrane recreates the action potential at its full amplitude as it travels down the axon, thus overcoming the limitations imposed by cable physics.

Taxonomic distribution

Action potentials are found throughout multicellular organisms, ranging from plants and invertebrates such as insects, to vertebrates such as reptiles and mammals. Sponges seem to be the main phylum of multi-cellular eukaryotes that does not transmit action potentials, although some studies have suggested that these organisms have a form of electrical signaling. The resting potential, as wel as the size and duration of the action potential, have not varied much with evolution, although the conduction velocity does vary dramatically with axonal diameter and myelination, as discussed in the Propagation section below.

Comparison of action potentials (APs) from a representative cross-section of animals

Animal	Cell type	Resting potential (mV)	AP increase (mV)	AP duration (ms)	Conduction speed (m/s)
Squid (Loligo)	Giant axon	-60	120	0.75	35
Earthworm (Lumbricus)	Median giant fiber	-70	100	1.0	30
Cockroach (Periplaneta)	Giant fiber	-70	80–104	0.4	10
Frog (Rana)	sciatic nerve axon	-60–80	110–130	1.0	7–30
Cat (Felis)	Spinal motor neuron	-55–80	80–110	1–1.5	30–120

In unmyelinated axons, action potentials propagate as an interaction between passively spreading membrane depolarization and voltage-gated sodium channels. When one patch of cell membrane is depolarized enough to open its voltage-gated sodium channels, sodium ions enter the cell by facilitated diffusion. Once inside, positively-charged sodium ions "nudge" adjacent ions down the axon by electrostatic repulsion (analogous to the principle behind Newton's cradle) and attract negative ions away from the adjacent membrane. As a result, a wave of positivity moves down the axon without any individual ion moving very far. Once the adjacent patch of membrane is depolarized, the voltage-gated sodium channels in that patch open, regenerating the cycle. The process repeats itself down the length of the axon, with an action potential regenerated at each segment of membrane.

Speed of propagation

See also: Time constant and Length constant

Action potentials propagate faster in axons of larger diameter, other things being equal. They typically travel from 10–100 m/s. The main reason is that the axial resistance of the axon lumen is lower with larger diameters, because of an increase in the ratio of cross-sectional area to membrane surface area. As the membrane surface area is the chief factor impeding action potential propagation in an unmyelinated axon, increasing this ratio is a particularly effective way of increasing conduction speed.

An extreme example of an animal using axon diameter to speed action potential conduction is found in the Atlantic squid. The squid giant axon controls the muscle contraction associated with the squid's predator escape response. This axon can be more than 1 mm in diameter, and is presumably an adaptation to allow very fast activation of the escape behavior. The velocity of nerve impulses in these fibers is among the fastest in nature. Squids are notable examples of organisms with unmyelinated axons; the first tests to try to determine the mechanism by which impulses travel along axons, involving the detection of a potential difference between the inside and the surface of a neuron, were undertaken in the 1940s by Alan Hodgkin and Andrew Huxley using squid giant axons because of their relatively large axon diameter. Hodgkin and Huxley won their shares of the 1963 Nobel Prize in Physiology or Medicine for their work on the electrophysiology of nerve action potentials.

In the autonomic nervous system in mammals, postganglionic neurons are unmyelinated. The small diameter of these axons (about 2 µ) results in a propagatory speed of approximately 1 m/s, as opposed to approximately 18 m/s in myelinated nerve fibers of comparable diameter, thus highlighting the effect of myelination on the speed of transmission of impulses.

Saltatory conduction

In myelinated axons, saltatory conduction is the process by which an action potential appears to jump along the length of an axon, being regenerated only at uninsulated segments (the nodes of Ranvier). Saltatory conduction increases nerve conduction velocity without having to dramatically increase axon diameter.

Saltatory conduction has played an important role in the evolution of larger and more complex organisms whose nervous systems must rapidly transmit action potentials across greater distances. Without saltatory conduction, conduction velocity would need large increases in axon diameter, resulting in organisms with nervous systems too large for their bodies.

Detailed mechanism

The main impediment to conduction speed in unmyelinated axons is membrane capacitance. In an electric circuit, the capacitance of a capacitor can be decreased by decreasing the cross-sectional area of its plates, or by increasing the distance between plates. The nervous system uses myelin as its main strategy to decrease membrane capacitance. Myelin is an insulating sheath wrapped around axons by Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes, in the Central Nervous System (CNS) neuroglia that flatten their cytoplasm to form large sheets made up mostly of plasma membrane. These sheets wrap around the axon, moving the conducting plates (the intra- and extracellular fluid) farther apart to decrease membrane capacitance.

The resulting insulation allows the rapid (essentially instantaneous) conduction of ions through a myelinated segment of axon, but prevents the regeneration of action potentials through those segments. Action potentials are only regenerated at the unmyelinated nodes of Ranvier which are spaced intermittently between myelinated segments. An abundance of voltage-gated sodium channels on these bare segments (up to three orders of magnitude greater than their density in unmyelinated axons) allows action potentials to be efficiently regenerated at the nodes of Ranvier.

As a result of myelination, the insulated portion of the axon behaves like a passive wire: it conducts action potentials rapidly because its membrane capacitance is low, and minimizes the degradation of action potentials because its membrane resistance is high. When this passively propagated signal reaches a node of Ranvier, it initiates an action potential, which subsequently travels passively to the next node where the cycle repeats.

Alternative models

The model of electrical signal propagation in neurons employing voltage-gated ion channels described above is accepted by almost all scientists working in the field. However there are a few observations not easily reconciled with the model:

• A signal traveling along a neuron is accompanied by a slight local thickening of the membrane and a force acting outwards.
• An action potential traveling along a neuron results in a slight increase in temperature followed by a decrease in temperature; electrical charges traveling through a resistor however always produce heat.

One recent alternative, the soliton model, attempts to explain signals in neurons as pressure (or sound) solitons traveling along the membrane, accompanied by electrical field changes resulting from piezo-electric effects.

Circuit model

A. A basic RC circuit superimposed on an image of a membrane bilayer shows the relationship between the two. B. More elaborate circuits can be used to model membranes containing ion channels, such as this one containing at channels for sodium (blue) and potassium (green).

Cell membranes that contain ion channels can be modeled as RC circuits to better understand the propagation of action potentials in biological membranes. In such a circuit, the resistor represents the membrane's ion channels, while the capacitor models the insulating lipid membrane. Variable resistors are used for voltage-gated ion channels, as their resistance changes with voltage. A fixed resistor represents the potassium leak channels that maintain the membrane's resting potential. The sodium and potassium gradients across the membrane are modeled as voltage sources (batteries).

Removed external links

Deleted links:

• Electrophysiology and The Molecular Basis of Excitability at University of Chicago -- animations didn't work for me, poor graphics

• Action Potential Len Kravitz, University of New Mexico -- too basic

• PSY 340 Brain and Behavior, 2.2a Neural Impulse (part 2) Vincent W. Hevern, Le Moyne College, Syracuse New York -- 404 error, page not found

• Action Potential Rachel McCready, Intensive Care Unit, London Health Services Centre -- too basic, might be misleading, not animated

• Propagation of an Action Potential National Health Museum Resource Center, Washington DC -- redudant with other chosen works, static

• Neurotransmission Steve Croker, University of Derby. Derby, England -- only an outline, no animations or explanations

• Neurotransmitter and neuron diagrams Edward I. Pollack, West Chester University of Pennsylvania -- 404 error, page not found

• Action Potential Conduction Encyclopædia Britannica -- overly brief, redundant; images good but unanimated

• Action Potential Frank Werblin, UC Berkeley. Animated and interactive tutorials -- beautiful, but I found these confusing

• Action Potential Movement Through an Axon at learner.org -- too basic; also doesn't explain at a glance