Expert: John Locke - 8/17/2007

Question
Hi it's me again.

Now I have question on the nervous system. I'm confused as to how an action potential is generated in a nerve and how it is propagated in a myelinated nerve. Could you help please?

Thanks

Answer
Thanks for using AllExperts, Shaazia.

I'm going to take a spatial view of what happens, from the dendrites on the nerve in question down to the synaptic knob. In doing so, I'll touch on all the major elements of the action potential process. First, let's recall exactly what nerve signaling does: it takes a chemical signal from the presynaptic nerve, converts it to an electrical signal in the form of an action potential, and then goes back to a chemical signal in the form of neurotransmitter release. Action potential is eventually abbreviated as AP here.

Start from the dendrites on the nerve we're interested in: neurotransmitters attach onto plasma membrane receptors and alter the cell's resting membrane voltage by opening or closing ion channels (the effect can be excitatory or inhibitory--that is, the neurotransmitters can alter the plasma membrane voltage closer to or farther from firing an action potential, respectively). The ion gates affected by neurotransmitters are termed chemically-gated ion channels, incidentally, and are almost entirely sodium ion channels. Neurotransmitters also attach to receptors on the cell soma, and it is the cumulative effect of all chemically-gated ion channels that controls whether an action potential will result.

Each neuron has a electrical threshold (termed the threshold voltage) beyond which an action potential will fire. It's an all-or-nothing response and a guaranteed response--an action potential always fires at the same strength, and it always fires once the threshold is reached. Repeated stimulation by neurotransmitter may open enough chemically-gated ion channels to reach that threshold voltage, at which point the chain reaction of an action potential takes over. The point where this reaction become self-sustaining occurs on the axon hillock, where there are enough electrically-gated sodium ion channels to actually sustain an AP. To repeat: neurotransmitters attach to the dendrites and cell body, and the cumulative effect of these stimuli can cause an AP to start on the axon hillock.

Once the threshold voltage has been reached, electrically-controlled ion channels begin to open. They will propagate the AP from this point on. Electrically-gated sodium ion channels open quickly, allowing sodium (which is in excess outside of the cell) to flow into the cell. This causes the inside of the cell to become positively charged relative to the outside--depolarization--and promotes a positive feedback loop by which adjacent sodium channels reach threshold and open. A "wave" of depolarization thus sweeps down the axon hillock, to the axon, and then to the synaptic knob. Now we must briefly discuss myelination.

As you probably know, myelinated neurons are coated in a protein fiber with periodic gaps along the axon. These gaps (the nodes of Ranvier) allow for saltatory or discontinuous depolarization: once an AP reaches a myelinated axon, it no longer moves in a continuous "wave" as it did on the axon hillock. Instead, depolarization only occurs at the nodes of Ranvier. The Na+ channels open at each node in sequence as you move down the axon--the depolarization from one node is actually strong enough to cause the channels at the next, downstream node to open. That node causes the next one in sequence to depolarize, and so forth. In this way the AP is propagated along the axon and eventually to the synaptic knob. Here, the AP causes the release of neurotransmitter by a mechanism that I will not review here.

How exactly does this saltatory conduction happen? Recall that sodium ions are flowing into the cell from each open ion channel; enough of these ions move passively from one node to the next to trigger the downstream sodium ion channels. That allows the AP (in the form of sodium ions) to move along the axon while the depolarization itself occurs only at the nodes of Ranvier.

Behind this wave of depolarization, other things are happening as well. Voltage-gated potassium channels started opening once the membrane voltage became positive, but they lagged behind the sodium channels. The influx of sodium causes the cell to reach a peak voltage, at which point the sodium channels are deactivated--not simply closed, but actually deactivated for a short time so that they can't operate at all (this also guarantees that the AP moves only in one direction). It is at this point that the potassium channels finally open, and potassium flows out of the cell, making the inside more negative relative to the outside, or repolarizing it. This also occurs in a "wave" behind that of the depolarization and is a very strong response, to the point that the neuron will become more negative than at rest (hyperpolarization). Potassium channels close and the neuron enters a "refractory period" where it physically cannot fire another AP--and for good reason, since potassium and sodium have reversed their concentration gradients to some extent. To remedy this, the sodium/potassium pumps actively transport sodium out of the cell and potassium into the cell until the resting potential is reestablished. At this point, the cell can fire another AP.

Here are two websites that demonstrate the overall reaction graphically, and many others will explain the same reaction textually and can be found via a simple Google search:

http://www.blackwellpublishing.com/matthews/channel.html
http://www.blackwellpublishing.com/matthews/actionp.html

Again, please feel free to email me with any other questions, and I wish you the best of luck.