EXCITABLE TISSUES: Action Potential Propagation

One of the important characteristics of action potentials is that they are able to travel (propagate) along excitable cells. The speed of propagation is fast and underpins the rapid communication that is enabled by excitable tissues. In this section we will have a look at some of the important aspects of action potential propagation. In order to simplify the story we will restrict our analysis to neurones (although many of the features are common to other excitable tissues).

Initiation

In neurones, action potentials appear to be initiated at a region of the axon just adjacent to the axon hillock that is known as the axon initial segment. This appears to be a consequence of the fact that this part of the membrane has a lower threshold than the rest of the cell. Consequently when the cell is stimulated, this part of the membrane reaches threshold before other parts, so the action potential is initiated here.

Propagation

Once initiated the action potential travels down the axon, away from the soma and towards the axon terminals. The speed of propagation can be easily determined by measuring the time that it takes for an action potential to travel a known distance and is known as the conduction velocity (usually expressed in m.sec^-1).

One of the variables that determines the conduction velocity of an axon is whether or not it has a myelin sheath. Let us have a look at the mechanism of propagation in axons with and without a myelin sheath.

Unmyelinated Axons

In axons without a myelin sheath the propagation of action potentials is a fairly simple affair. The presence of the action potential in the membrane triggers the opening of voltage-gated Na⁺ channels in the adjacent membrane. The voltage sensors in these channels detect the rapidly depolarisation of the membrane nearby and simply do what they are programmed to do and open. As a result Na⁺, rushes into the cell and initiates the action potential further along the axon. In other words the close apposition of the voltage-gated Na⁺ channels enables those downstream to see the action potential in the adjacent membrane and effectively replicate it in the portion of membrane where they are located.

The diagram opposite shows the membrane potential recorded at three different points along the length of an axon and the status of the adjacent voltage-gated Na⁺ channels. Place the cursor on the image to start the animation.

Animation showing how the action potential travels along an unmyelinated axon

We tend to think about the individual events that go to form an action potential as being fairly rapid. However if we consider the time that it takes for the individual ion channels to detect the change in membrane potential, produce the change in shape that enable opening and then for the ions to actually move, these add up to a small but significant delay in the movement of action potentials along unmyelinated axons. For this reason the conduction velocity of unmyelinated axons is relatively slow and typically in the range of 0.5 - 2.5 m.sec^-1 in mammals.

Myelinated Axons

Myelinated axons are wrapped in a thick myelin sheath with regular gaps (known as nodes of Ranvier) where the enclosed axon is exposed. Action potential propagation along the nodes is exactly the same as it is for unmyelinated axons (describe above) and so is relatively slow.

However the presence of the heavy insulation formed by the myelin sheath enable voltage-gated Na⁺ channels to detect the voltage of the action potential in the adjacent node. This enables the action potential to jump, virtually instantaneously from node to node. This type of conduction is referred to as saltatory conduction.

So in myelinated axons we get normal relatively slow propagation of action potentials along nodes but very rapid (saltatory) conduction between nodes. The net effect of this mechanism is that the conduction velocity of action potentials is very much quicker in myelinated axons (12 - 130 m.sec^-1).

Refractory Periods

Another important feature that keeps action potentials moving along the axon in one direction (i.e. away from the soma and towards the axon terminals) is that the region of the axon that the action potential has just passed through becomes refractory (inactive) for a short period of time. During this time it is difficult to initiate action potentials in this part of the axon so the action potential can only go in one direction.

You can demonstrate this phenomenon in a fairly simple experiment that is simulated in the diagram opposite.

If you stimulate a neurone with a stimulus (S1) that is sufficiently intense to produce an action potential and then after a few milliseconds stimulate it again (S2) you observe two normal action potentials.

However if you reduce the interval (delay) between the two stimuli (using the adjacent +/- buttons) then you can observe what we refer to as refractory periods.

interactive animation showing the impact of changing the delay between two stimuli on the height of the second action potential

There are actually two distinct phases of the refractory period:

Absolute Refractory Period

The period where the second stimulus applied to the cell fails to produce and action potential is known as the absolute refractory period. It does not matter what you do to the cell at this point you can not produce an action potential. In the diagram opposite the first stimulus (S1) produces an action potential but the two subsequent stimuli (S2 & S3) fail to produce an action potential because they fall within the absolute refractory period.

The absolute refractory period is caused by the fact that once the voltage-gated Na⁺ channels that are responsible for the depolarising phase of the action potential have opened and then closed again they are effectively “jammed shut” for a short period of time. This jamming of the Na⁺ channels appears to be a consequence of their molecular structure and is known as Na⁺ channel inactivation. During this time there is nothing that you can do to open those channels again so we cannot produce an action potential in the cell.

$Graphic showing the absolute refractory period$

Relative Refractory Period

As we increase the delay between our two stimuli and move out of the absolute refractory period we see a small action potential that gradually increases in size as the delay increases. This period is known as the relative refractory period and is characterised by an action potential of reduced amplitude. (I know that I have stressed previously that action potentials within a particular type of cell are always the same size so it is important to remember that we are talking about an experimental situation here).

The relative refractory is caused by the gradual recovery of the voltage-gated Na⁺ channels from inactivation. As more and more of these Na⁺ channels come out of inactivation, more and more of them can be opened by the stimulus and more and more Na⁺ can flow into the cell. Because Na⁺ influx is responsible for the depolarising phase of the action potential the greater the influx of Na⁺ the bigger the action potential.

$Graphic showing the relative refractory period$

So to summarise, it is Na⁺ channel inactivation that is responsible for the absolute refractory period and the progressive recovery from Na⁺ channel inactivation that results in the relative refractory period.

Refractory periods have two important physiological consequences:

1. They ensure that action potentials travel along axons in one direction. Refractory periods mean that the part of the membrane where the action potential has just been is inactive for a short period of time.

2. They limit the action potential frequency in neurones. Stimuli that produce action potentials much above 300 Hz (300 action potentials per second) produce inter stimulus intervals that are starting to get into the refractory period and are therefore blocked.

Local Anaesthetics

Local anaesthetics are a class of drug that are used to anaesthetise regions of the body during surgical procedures and include substances such as Xylocaine and Lidocaine. They are usually injected around a nerve and reversibly block propagation of action potentials through this nerve. Consequently they abolish sensations arising from the part of the body innervated by this nerve and it feels numb.

Local anaesthetics prevent action potential propagation by blocking voltage-gated sodium channels. In the presence of this blockage sodium is unable to enter the cell and so the depolarising phase cannot occur and the action potential is prevented from occurring.