Electrical Changes during the Action Potential

The axon has two states: resting and active. When the neurone is inactive the transmembrane potential is called the resting potential (nominally -70mV). When the nerve becomes active, it sends trains of short electrical pulses, called action potentials, to the end of the axon. Each action potential lasts ~1 millisecond during which the transmembrane potential is reversed, and these impulses are conducted - travel - along the axon at high speed (up to 120 m/sec), related to the diameter of the axon.

Recording of action potentials can be done in two ways: action potentials in single axons requires microelectrodes that penetrate the nerve cell membrane, and second, the compound action potential can be recorded using external electrodes applied to a nerve containing many axons. The first method allows the mechanisms that generate action potentials to be studied; the compound action potential is useful to identify the different types of axons, and to study the condition of human nerves.

Action Potentials

Action potentials are generated when voltage-gated sodium channels open as a result of the passage of local electrical currents across the membrane.

These local currents may occur at the site of

• an electrical stimulus
• a depolarisation produced by a generator potential at a sensory ending
• a depolarisation of the cell body produced by an EPSP (excitatory post-synaptic potential)
• a depolarisation produced by ligand-gated channels (receptors) on a post-synaptic membrane

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Whenever a depolarization of the axon is sufficient to reach a threshold (when the resting potential drops to around - 50 to -55 mv), voltage-sensitive sodium channels in the membrane open. As a consequence some Na⁺  ions move down both electrical and voltage gradients towards the Na⁺ equilibrium potential (about +40 to +60 mV) and cause the membrane potential to reverse for less than a millisecond.

The All or Nothing Law (which applies to single axons) states that an electrical stimulus of a particular size to an axon either produces an action potential or it does not.

The Threshold stimulus is the stimulus size (mV or mA) that just initiates an action potential

A stimulus that is insufficient to initiate an action potential is known as a Subthreshold Stimulus

A stimulus greater than the threshold stimulus is called a Suprathreshold stimulus: the action potential is no different from that induced by a threshold stimulus and the swing of membrane potential is constant in size

This diagram shows the electrical changes during the action potential, elicited in response to a local potential reaching threshold.

Strength-Duration Curve and Refractory Period   Top

Strength-Duration Curve

There is relationship between the strength of the stimulation current required to produce an action potential in a single axon, and the duration of that current.

At longer the durations of stimulating current, less current is require to elicit an action potential.

The strength-duration curve plots the relationship between these two variables.

The hyperbolic shape of the graph shows the amount of current and its duration required to reach threshold. High currents require a shorter time to reach threshold. Lower currents require more time to reach threshold.

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Refractory Period

Following an action potential (AP) there is a short period of time (~1 msec) during which the nerve is refractory: i.e. it is irresponsive or less responsive to electrical stimuli. This is the time at which the voltage gated sodium channels are returning to their normal conformation (the channels are 'inactivated').

The Absolute Refractory Period is the period after the AP during which the nerve cannot be re-excited by electrical stimulation, no matter how large the stimulus. This is because Na⁺ channels are totally inactivated.

In the Relative Refractory Period, a second AP can be initiated, but only by using larger stimulating currents. This is because some Na⁺ channels are still inactivated, while others are activated.

Ionic Movements during the Action Potential

Ionic Movements during the Action Potential

When a threshold or suprathreshold stimulus is delivered to the neurone, the membrane becomes depolarised, voltage gated sodium channels open and allow some sodium ions to enter the neurone, because of (a) the concentration gradient of sodium, and (b) the negative potential within the axon which attracts the positively charged ion.

When the action potential is near its peak, Na⁺ channels become inactivated (close), and K⁺ channels open and allow some K⁺ ions to leave the cell causing repolarisation and hyperpolarisation of the membrane.

The sodium-potassium pump works continuously and over the course of time the ionic concentrations inside the axon return to normal. Large numbers of action potentials can occur without significantly altering the internal concentration of the ions.

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When a device injects current into or out of the axon (using a microelectrode) so as to maintain a constant membrane potentiak, the current injected is a measure of the flow of current into or out of the axon. This method is called Voltage Clamping, and when the axon is clamped at a constant potential, the ions that carry the current flowing can be analysed by changing the ionic gradients of the ions involved. Thus the size of the sodium current and the potassium current during the action potential can be calculated, and the diagram opposite is the result of these voltage clamp experiments. It shows the time course of changes in permeability for sodium and potassium: early in the action potential (shown again the scale calibrated in mV) there is a marked increase in permeability to sodium, and this is followed by a smaller but longer increase in potassium permeability. This is the basis for the statement that during the action potential, some sodium ions move into the axon then some potassium ions move out of the axon. The numbers of ions involved are actually excedingly small.

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There are several types of voltage-gated sodium channels in electrically excitable tissues, called Nav channels (subtypes 1.1 thru 1.9). These are heteromeric complexes consisting of a large central pore-the alpha subunit - and 2 smaller auxiliary beta subunits. The structurally distinct isofoms give rise to the ion channels in muscle and cardiac muscle (Nav1.4 and 1.5) as well as in nerve. In the brain there is a subfamily of isoforms (Nav1.1, 1.2 and 1.3)

Nav1.7 is expressed particularly in the small dorsal root ganglion (sensory) neurones and in the autonomic ganglia.

Nav1.8 and 1.9 inactivate more slowly than Nav1.7, and this difference is likely to affect the generation and propagation of action potentials, and alter transmitter release at nerve terminals. Nav1.8 is known to be involved in hyperalgesia and allodynia in experimental investigations; studies of Nav1.8 knockout mice have shown that the channel is associated with inflammatory and neuropathic pain. The presence of Nav1.9 is associated with hypersensitivity to heat and mecahnical stimuli in inflammatory pain.