Video: Action potential

No matter how advanced or sophisticated technology seems to be becoming in the world today, at its most basic level, it is all still fundamentally based on the basic language of binary code. All the images and graphics in this amazing video, to this recording of my smooth Australian accent, are basically representations of zeros and ones sequenced in binary code.

Our nervous system uses a not too dissimilar form of binary communication to convey messages throughout the body. Just as binary code translates into diverse digital functions, action potentials are the basic electrical impulses that carry information through neurons. By varying their patterns and frequencies. just like the zeros and ones of binary code, these signals encode everything from gentle sensations on your fingertips to solving complex problems, making memories or experiencing any emotion you can think of.

They are all possible due to electric signals known as action potentials.

Before we look at how these electrical impulses are being generated, let's remind ourselves about some basics of neuron electrophysiology.

The first is the basic structure of a neuron. You'll remember they have three main parts: a cell body containing a nucleus; dendrites, which are the tree-like processes representing the receptive or input part of the neuron; and the axon, which represent the transmitting or output part of the neuron. These can be very long, as they often need to transmit information over long distances.

Action potentials are generated at the axon hillock of the cell body as well as the initial segment of the axon. This area is called the trigger zone.

The second is the concept of membrane potential. At rest, when no electrical signals are being generated or conducted, the cell membrane of the neuron has a resting membrane potential of approximately -70 millivolts. This means the inside of the neuron is more negatively charged relative to the outside due to the distribution of charged particles, such as ions along the cell membrane.

Next, we need to remind ourselves that the conditions and initiation of a neuronal signal are dependent on the movement of ions, which are distributed unequally between the intracellular and extracellular environments of the neuron.

Sodium and calcium ions are high concentration outside the neuron and therefore want to enter the neuron when possible. When this happens, the membrane potential becomes more positive. Chloride ions, which are negatively charged, are also in high concentration outside the neuron; however, when they enter the neuron, they cause the membrane potential to become more negative. Finally, potassium ions are in high concentration inside the neuron and therefore want to leave the neuron. When this happens, this also makes the membrane potential more negative.

Ions cannot simply move across the cell membrane at will. Instead, they need a protein embedded in the membrane to facilitate their movement. One way for ions to cross the cell membrane are ion channels which are openings in the cell membrane, allowing ions to move by passive diffusion along their electrochemical gradient. Some ion channels are always open, but others require a signal to tell them to open or close. You'll see that voltage-gated channels will play a major role in action potentials. They open and close in response to changes in membrane potential.

If you need to brush up on any of these concepts, be sure to first check out our video on the introduction to neuron electrophysiology before you continue on to learn about the ins and outs of action potential.

All right, time to look at the individual steps of how an action potential is formed. How is this achieved? Well, first, an excitatory stimulus will usually cause either sodium or calcium ion channels in the cell membrane to open, allowing them to move into the neuron. This initial phase, with the addition of positively-charged ions to the intracellular environment, is sometimes referred to as hypopolarization, as it causes the membrane potential to become less negative or less polarized.

An example of such an excitatory stimulus in this case could be mechanical pressure being applied to the cell membrane resulting in the opening of mechanically-gated ion channels. Or it could be a chemical messenger, like a neurotransmitter, that either directly binds to a receptor on the ion channel or a receptor nearby, causing the ion channels to open and allow specific ions to flow into the neuron.

The initial change in membrane potential from this excitatory stimulus is generally small, and we call this a local potential. Local potentials can vary in size and they can actually make the membrane potential less or more negative, but we'll just consider those which make it less negative for now. When a local potential occurs, it is a short-lived event as the neuron moves quickly to restore its membrane potential to resting values.

Local potentials, however, can be combined or summed, which means several of them can cumulatively bring about a greater change in membrane potential. So, if a stimulus is repeated over and over in a short space of time or if many stimuli are received simultaneously, it can result in a larger displacement of the resting membrane potential which moves towards a threshold membrane potential of -55 millivolts.

If, and only if, the local potentials collectively raise the membrane potential to around -55 millivolts, or threshold, this is when things get exciting, and an action potential is fired. At rest, the voltage-gated sodium ion channels are closed. Once the membrane potential reaches the threshold membrane potential, these channels will open.

The electrochemical gradient of sodium ions causes them to rush into the neuron as sodium ions will move from areas of high to low concentration, and because they are positively charged, they will also be drawn into the neuron which is relatively more negative intracellularly. This rush of positive ions into the neuron triggers depolarization of the cell membrane, meaning the membrane potential moves towards 0 millivolts.

The chemical gradient for sodium ions is so strong that they will continue to enter the cell even after the membrane potential has reached 0 millivolts and the electrical gradient has reversed, so the membrane potential will continue to become more positive. This is called an overshoot.

The membrane potential will always peak at about 30 millivolts, regardless of the strength of the initial stimulus which triggered the action potential. At this stage, the voltage-gated sodium channels will have become inactivated and the inward flow of sodium ions will stop. Let's look at this step a little closer.

Voltage-gated sodium ion channels usually have two gates: an activation gate and an inactivation gate. The activation gate opens quickly when the threshold membrane potential is reached and allows sodium ions to pass to the intracellular fluid. However, the same change in membrane potential also causes the inactivation gate to close, albeit at a slower rate than the activation gate. This allows just enough sodium ions to cross the cell membrane for the action potential to peak at about 30 millivolts and also ensures that the action potential is brief.

Now at the same time as the voltage-gated sodium channels open, other voltage-gated ion channels, specific for potassium ions, will also open in the cell membrane. However, they are much slower to open. By the time the sodium ion channels have become inactivated at the peak of the action potential, the potassium ion channels have only finished opening.

At this time, the relatively positive intracellular environment, created due to the brief influx of sodium ions as well as chemical gradient of potassium ions, pushes potassium ions out of the neuron. As they are positively charged, that means the membrane potential begins to move back towards its resting value of -70 millivolts. This is called repolarization.

As the membrane potential reaches its resting value, the voltage-gated potassium ion channels are still at work here. These will eventually become inactivated, once their inactivation gate has closed. The closure of the inactivation gate is slower than the opening of the activation gate, resulting in the cell membrane becoming hyperpolarized as potassium ions continue to leave the neuron. This dip in membrane potential is also known as undershoot.

Ultimately, the closure of the inactivation gate of potassium ion channels will prevent the membrane potential from being more negative. It's important to note at this stage that although action potentials are caused by the movement of ions, the number of ions which actually move across the cell membrane is relatively small, therefore, the overall concentrations of those ions inside and outside the cell are not changed during one or even several action potentials.

Ions which do move into or out of the cells are relatively quickly restored to their original environments by the sodium-potassium pump. You'll remember that the pump does this by transporting three sodium ions out of the neuron and two potassium ions into the neuron against their concentration gradients. Since the voltage-gated ion channels are now closed, the action of the sodium-potassium pump, as well as leakage ion channels for potassium and sodium, creates the conditions for the resting membrane potential to be restored back to -70 millivolts, until the next action potential.

We've seen now how action potentials are generated and the steps involved. Let's now look at how often this can happen.

Once an action potential has been initiated, neurons are limited for a brief period of time in their ability to fire another one. This brief period of time is known as a refractory period. The refractory period is divided into two parts: an absolute refractory period and a relative refractory period.

During the absolute refractory period, once an action potential has been initiated, a neuron cannot fire another action potential for a defined period of time, no matter how strong the stimulus. This is primarily due to the closing of the inactivation gate of the voltage-gated sodium ion channels. So the absolute refractory period represents the time needed for the inactivation gate to open, which occurs as the membrane potential shifts towards its resting value.

The absolute refractory period lasts about 1 to 2 milliseconds and prevents action potentials from happening again too quickly. It also prevents action potentials from traveling backwards along the axon.

The relative refractory period occurs during the hyperpolarization phase of the action potential. Here, the activation gate of the voltage-gated sodium ion channels is closed, but the inactivation gate is open. This means that a second action potential can potentially be initiated. However, due to the more negative membrane potential at this time caused by the voltage-gated potassium channels that is still open, a greater stimulus will be required to depolarize the membrane potential enough to reach the threshold potential of -55 millivolts. So here, action potentials can occur, it just takes a little more work to get there.

After having spoken about both local potentials and action potentials, let's review some important differences between them.

The first point to emphasize is that all action potentials are subject to what is called the all-or-nothing law, which means an action potential is either initiated and completed in full or it is not, depending on whether the threshold potential is reached, and it always depolarizes the cell membrane. Local potentials are not subject to this and can result in both depolarization or hyperpolarization.

Local potentials generally reflect the strength of the stimulus behind them: a bigger stimulus elicits a bigger change in membrane potential. The properties of an action potential, however, are always the same and are not changed by the strength, frequency, or length of the initial stimulus. The result of an action potential is always the same. It will depolarize the cell membrane to a maximum of about 30 millivolts.

The final difference between local and action potentials is that local potentials diminish and dissipate over short distances. Action potentials, on the other hand, can be carried over long distances without losing strength and cannot be stopped once triggered. We'll see why this is the case in just a moment.

So that covers a lot of the stages and properties of an action potential. Let's take some time now to look at how action potentials are propagated or conducted along the axon.

So we know that action potentials are generated at the axon hillock and initial segment of the axon, also known as trigger zone. However, we also know that they need to be propagated or conducted without diminishing along the length of the sometimes very long axons to the axon terminals, where the neuronal synapses can be found. We can distinguish between two types of action potential conduction which depends on the presence of a myelin sheath around the axon.

When myelination is present, the action potential propagates differently and the speed of signal propagation is optimized. Conduction along a nonmyelinated axon is referred to as continuous conduction, while conduction along a myelinated axon is referred to as saltatory conduction. Let's begin with continuous conduction.

First, the cell membrane of the neuron in the region of the axon hillock and initial segment of the axon is depolarized to threshold due to local potentials coming from the dendrites or cell body. When this occurs, we know that voltage-gated sodium ion channels are activated and the action potential is triggered, causing full depolarization of the cell membrane at this part of the axon.

The depolarizing current then spreads to an adjacent part of the cell membrane, causing it to also depolarize to threshold. This causes voltage-gated sodium ion channels in this area to activate, and another action potential to be triggered here. From here, the process will repeat again and again. Each action potential propagates another action potential, kind of like a domino effect which cannot be stopped until it reaches the end of the axon.

Now one important thing to note is that although the depolarizing current from an action potential may flow backwards into the direction of the trigger zone, it will have no effect on the cell membrane here. This is because this section will have just completed an action potential and be in its absolute refractory period, where the voltage-gated sodium ion channels are inactivated. This ensures that action potentials only travel in one direction.

Time to take a look now at saltatory conduction, which is significantly faster. You'll remember that I mentioned that saltatory conduction occurs in neurons which are myelinated.

In the central nervous system, the myelin sheath is generated by oligodendrocytes, while in the peripheral nervous system, it is formed by Schwann cells. In either case, there are small interruptions in the myelin sheath called myelin sheath gaps or nodes of Ranvier, which are rich in voltage-gated sodium ion channels.

So with saltatory conduction, the basic principle which we saw in continuous conduction where one action potential propagates another, still stands. The difference here is the distance between regions dense in voltage-gated ion channels where action potentials arise. You'll remember that in a nonmyelinated axon, the entire length of the axon is covered in these channels. In a myelinated axon, however, there are no voltage-gated sodium ion channels where the myelin sheath is present.

When an action potential is generated at the trigger zone, it generates a depolarizing current which can passively flow further along the axon, with little loss of charge, as far as the first myelin sheath gap. When the current reaches this point, it depolarizes the cell membrane, activating the voltage-gated sodium ion channels and another action potential is generated, which passes to the next myelin sheath gap and so on.

The preservation of the signal strength from one myelin sheath gap to the next is achieved due to the excellent insulating properties of the myelin sheath, which prevents ion leakage across the cell membrane of the neuron, ensuring the reliable longer-distance transmission of current. To saltate means to move by leaps or jumps, similar to how an action potential will propagate down an axon. It jumps from one myelin sheath gap to the next, where a new action potential is generated at each gap.

There are many benefits to this type of conduction. First of all, saltatory conduction is metabolically more efficient since ion channels only need to be present at the myelin sheath gaps and not along the entire axon. This means that ion exchange only occurs at these sites. This reduces the energy cost for the neuron as fewer sodium-potassium pumps are required to replace sodium and potassium ions back to their original compartments, against their concentration gradients.

Secondly, because there are fewer ion channels involved in conducting the action potential along the length of the axon, less time is spent opening ion channels, which makes the overall process much faster compared to continuous conduction.

In addition to myelination, another factor which influences the speed of conduction is the diameter of the axon in question. Axons with a larger diameter have a larger conduction velocity, which means that they are able to send signals faster. With more space inside the axon, ions can travel more freely and are less likely to encounter obstacles or resistance that could disrupt their path.

Since the axon is filled with cytoplasmic components like proteins and vesicles, a larger diameter reduces the chances of these ions colliding with such elements and being slowed down. Think of it like driving on a road: a wider road allows you to drive faster and pass obstacles compared to a narrow road, where driving is more constrained and slower.

Lastly, it is worth mentioning that there is a correlation between axon diameter and myelination. Thicker axons with a diameter greater than 1 millimeter are generally myelinated. The largest of these are known as type A fibers and are involved in motor control, touch, pressure, and proprioception. They can conduct action potentials at a speed of up to 120 meters per second.

Intermediate-sized fibers, known as type B fibers, are also myelinated, albeit less so than type A, and are primarily involved in autonomic functions. They conduct action potential somewhat slower, between 10 and 15 meters per second.

The thinnest axons are nonmyelinated. These typically have a diameter of less than 1 micron and are often called C fibers. These can be found in neurons that carry slow pain and temperature information from the skin to the spinal cord to produce the sensation of dull, diffuse, aching, burning, and delayed pain. They propagate action potentials the slowest, with a speed of approximately 1 meter per second.

And that concludes our tutorial for today. We discussed how action potentials are generated and looked at the different factors affecting their propagation and conduction velocity.

To revise this content, check out our quiz and other learning materials in our study unit on this topic.

See you next time!