Action Potentials
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Introduction
Action potentials are transient, regenerative electrical impulses in which membrane potential (Vm) rises approximately 100 mV above the negative resting potential (Vrest). In a naked axon, transmission speed is ~ 1 m/s, while myelinated axons are about 90 m/s.
Action potentials are begun in the inial segment of the axon, an unmyelinated area referred to as the 'spike initiation zone'.
Resting Potential
Skeletal muscle cells, cardiac cells, and neurons typically have a resting potential of -70 mV.
Membrane potential is generated by ion gradients. This is maintained by action of the sodium-potassium exchanger, which exports 3 Na+ for every 2 K+, resulting in net movement of one positive charge outside the cell.
Depolarization
Influx of positive ions (current) causes the cell to become more positive. This electronic potential will spread passively through the cell and will decay over the cell's length due to loss of energy.
As a stimulus increases in magnitude or in duration, the cell becomes more positive, and thereshold is reached. At this point, voltage-gated sodium channels open and an action potential begins. This all-or-nothing event travels along the cell without decaying.
Action potentials vary in shape and amplitude according to cell function. A nerve axon will have a brief signal, while the rhythmic contraction of cardiac tissue uses prolonged, repetitive action potentials.
Types of Action Potentials
Each type of neuron has its own shape and height to its APs. The largest variation occurs in the repolarization phase, mediated by delayed Ca influx and various K+ efflux.
Repetition of action potentials can induce adaptation of various strengths or bursts of APs. Rhythmically bursting cells can participate in central pattern generators of respiration or locomotion. Other bursting cells can release hormones or mediate body rhythmns.
Firing patterns are determined by a variety of ion currents, primarily slowly changing ones.
Axon potentials are quite affected by temperature; MS can do well with cold baths.
Ion Flow
The Nernst equation determines equilibrium based on outside and inside concentrations of a given ion.
For K+, the equation states
Ek = 62 mV (log [K]out / [K]in)
|
[out] |
[in] |
eq |
K+ |
4 mM |
130 mM |
-94 mV |
Na+ |
140 mM |
15 mM |
+60 mV |
Ca2+ |
2.5 mM |
0.0001 mM |
+136 mV |
Cl- |
120 mM |
5 mM |
-86 mV |
These high concentration gradients require ATPases to maintain them in the face of leak.
Ion flow always travels down the concentration gradient.
After a few minutes of blood loss to the brain, ATP production drops, the cell depolarizes, calcium enters, and the cell can die.
Refractory period
After one AP fires, a certain amount of time needs to pass before another can be triggered.
The refractory period limits firing frequency, and is determined initially by sodium channel inactivation and then K channel opening. The absolute refractory period prevents all APs, while the relative refractory period which follows requires higher than normal stimulus strength.
Firing rates
Given an AP of 1 microsecond, one can have (theoretically) 1000 in a second, or 1000 Hz. Neurons in the ear can keep up with this.
Passive Charging
ion flow can
Passive discharging
Passive properties decrease current flow along a neuron, including length (λ) and time.
Flow will dissipate exponentially; after 100 micrometres, it is gone without ion influx. Flow also dissipates according to time and
Action Potential Propogation
A self regenerating signal occurs as sequential areas of membrane reach threshold and are depolarized.
Local circuit currents become set up as ion flow travels both through the intracellular and extracellular medium.
As nerve fibres are inherently leaky due to background channel conductivity, current is passively lost over distance. Two strategies are used to improve conduction: increase axon diameter, and myelination to increase electical conduction.
Nodes of Ranvier
In myelinated nerves, the myelin sheath is interrupted at regular intervals by short (1 um) uncovered regions called nodes of Ranvier. Internodal length ranges from 0.2 - 2 mm.
In between areas covered with myelin, Nodes of Ranvier are areas of axonal membrane rich in NA+ channels (approximately 1000/um2), compared to myelinated areas of less than 25/um2). Conversely, K+ channels are present at higher densities under the myelin sheath.
Saltatory Conduction
Following excitation at a given node, a threshold for excitation at the next node is reach in approximately 20 μsec
Neuron Ion Channels
There are various membrane channels in neurons. And these are incredible targets for drugs and toxins.
Voltage-Gated Channels
Sodium channels
As a cell reaches threshold, voltage-gated sodium channels, which normally remain closed, open very briefly. This produces the initial depolarizing phase. Sodium influx is affected by [Na] and also by [Ca]. As [Ca2+]o becomes progressively higher, the threshold for channel opening becomes higher as well.
CC: hypoparathyroidism (high [Ca2+] ) or hyperparathyroidism (low [Ca2+] ) can seriously affect neurological symptoms; the latter can cause hyperexcitiability.
Voltage-gated channels close very quickly, on their own. This leads to the refractory period as the channel is slowly reversed by a return to a negative state inside the cell.
Na channels can be blocked by neurotoxins such as TTX (from pufferfish) and by local anaesthetics including cocaine, lidocaine, and procaine. These drugs are use-dependent, meaning channels must be activated before the drugs can bind.
Potassium channels
We have at least 38 distinct genes encoding potassium channels.
The primary role of K in excitable cells is inhibitory, opposing the action of Na+ and Ca2+ and keeping the cell in its resting, nonexcited state.
There are four major types of K currents:
- delayed outward (Kv family)
- transient outward (Kv family)
- Ca2+-activated (KCa family)
- inward (IR family)
Calcium channels
L-type calcium channels are long lived, residing in the heart, skeletal muscle, neurons, and smooth muscle.
Ligand-Gated Channels
Ligand-gated ion channels have ligand binding sites directly on the channel, as compared with metabotropic ion channels that interact with receptors through g proteins or 2nd messengers. Metabotropic channels show amplification.
Nicotinic ACh Receptor
GABAA Receptor
Glycine Receptor
AMPA Receptor
In a condition called hyperkalemic peroidic paralysis, too much K leads to an increased [K]in and increases Na channel re-opening.
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