Step 3: The Action Potential

So now you should know how a neuron establishes the electrochemical gradient it uses for signaling. But how does it actually use this gradient to create signals?

It is through the combination of various channels and pumps that the neuron controls the flow of ions and thus creates signals. So basically neuronal signals are just ions flowing across the neuron's membrane. When ions, or charged particles move it is a current, like electricity in a wire. We will examine an Action Potential (AP) traveling in an axon as a an example of the entire process.

The most important players in the AP are the voltage-gated ion channels for Na+ and K+. An axon (& only the axon) is loaded with these channels (in myelinated neurons they are all concentrated at the Nodes of Ranvier). Voltage-gated channels have evolved so that they only open when the voltage or potential inside the neuron becomes more + than the resting potential. When the neuron’s potential becomes more positive than its resting potential, the neuron is said to be depolarized. One major difference between voltage-gated Na+ channels and voltage-gated K+ channels is that Na+ channels open and close very quickly, but K+ channels open and close very slowly. So, even though they both respond to the same stimulus (a depolarization), Na+ channels are opening and allowing Na+ in much sooner than K+ channels are opening and allowing K+ out. Why does Na+ go in and K+ go out? Always keep in mind the resting neuron--inside the cell it is very negative, Na+ is in very low concentration, and K+ is in very high concentration. So Na+ wants to rush into the cell based on its concentration gradient and it also wants to rush in because it is a + ion and it is electrically attracted to the negativity on the inside of the cell. Now, if Na+ always rushes in first because it has fast channels, then that makes the negativity inside the cell go away and if enough Na+ comes in, the potential inside the cell will actually go +. Then, as more of the slow K+ channels open and K+ has a driving force pushing it out of the cell due to its concentration gradient and it also has a driving force pushing it out of the cell because now the cell is + inside and + ions are repelled by + charge. By the time K+ is in full force rushing out, the Na+ channels have closed, so K+ will rush out until the cell becomes so negative inside that the electrical force pulling K+ back in balances out the force from the concentration gradient driving K+ out. Then the K+ channels close and all ions cease any net movement (other than a few K+ out of leak channels).

An AP begins at the axon hillock / initial segment of an axon when the neuron’s threshold is reached. The threshold is a potential more + than the resting potential that opens enough voltage-gated Na+ channels such that some Na+ comes in, which makes the potential even more positive, which opens even more voltage-gated Na+ channels and so on and so on (the positive feedback cycle). After threshold is reached and an AP is generated, it is propagated down the axon toward the axon terminal. The process described above happens in sequential fashion as the AP moves along the axon. However, the AP can propagate only if there are enough closely spaced voltage-gated channels spaced out along the axon. In myelinated neurons voltage-gated channels are clustered at the Nodes of Ranvier. Since these nodes are spaced out along the axon by myelin sheaths, the AP appears to jump from node to node. This is known as saltatory conduction. Even though the AP would appear to jump from node to node, the depolarization is actually spreading inside the axon so that the effects of incoming Na+ (depolarization) at one node are eventually detected at a neighboring node, causing the opening of voltage-gated channels.

An AP traveling down an axon is like a line of dominos.

Synaptic Transmission

When the AP reaches the axon terminal, the terminal is depolarized. In chemical synapses, this stimulates the opening of voltage-gated Ca+2 channels found exclusively at the axon terminal. Ca+2 is in relatively high concentration outside the neuron, as it is in all cells, so when the voltage-gated channels open, Ca+2 rushes in. The presence of Ca+2 in the axon terminal causes synaptic vesicles in the terminal to fuse with the neuron’s membrane and exocytose their contents (neurotransmitters). These neurotransmitters slowly travel across the synaptic cleft until they reach a receptor on a post-synaptic cell. When the receptors have bound their corresponding neurotransmitters, this opens ion channels on the post-synaptic cell membrane. Ions flow into the post-synaptic cell and thus, change it's membrane potential. Depending on the ions that flow across the post-synaptic cell membrane, the cell will either be excited (if the membrane is depolarized) or inhibited (if the membrane is hyperpolarized).

Now watch the animation of the AP traveling down the axon and causing neurotransmitter release.

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Note the symbol key below before you start the animation:

Notice you can pause and play the movie at any point along the way.