12.4 The Action Potential

Membrane Potential and Action Potentials

Ion channels and resting potential

The resting membrane potential is the voltage difference across a neuron's membrane when the neuron is not firing. It sits at roughly -70 mV, meaning the inside of the cell is more negative than the outside.

Two major ion gradients create this charge difference:

• $K^+$ is concentrated inside the cell
• $Na^+$ is concentrated outside the cell

These gradients don't just exist on their own. They're actively maintained and passively expressed through specific membrane proteins:

• $K^+$ leak channels are the most numerous leak channels in a resting neuron. They let $K^+$ diffuse out of the cell down its concentration gradient, which makes the inside of the cell more negative.
• $Na^+$ leak channels allow a small amount of $Na^+$ to trickle in, slightly offsetting the negativity, but there are far fewer of these than $K^+$ leak channels.
• The $Na^+/K^+$ ATPase pump actively moves 3 $Na^+$ out and 2 $K^+$ in for every ATP molecule consumed. Because it exports more positive charges than it imports, the pump itself is electrogenic and contributes a small amount to the negative resting potential. More importantly, it restores the ion gradients that leak channels constantly run down.

The resting potential is therefore set primarily by $K^+$ permeability, with the pump working in the background to keep the concentration gradients stable.

Sequence of action potential generation

An action potential is a rapid, all-or-nothing reversal of membrane voltage that travels along the axon. Here's how it unfolds:

1. Stimulus and threshold: A stimulus (from a receptor, another neuron, etc.) depolarizes the membrane, making it less negative. If the membrane reaches threshold (approximately -55 mV), an action potential is triggered. Stimuli that fall short of threshold produce only local, graded potentials that die out.

2. Rising phase (depolarization): Voltage-gated $Na^+$ channels snap open. $Na^+$ rushes into the cell down both its concentration gradient and the electrical gradient. This drives the membrane potential rapidly upward, overshooting zero and peaking near +30 mV.

3. Falling phase (repolarization): Two things happen almost simultaneously. The voltage-gated $Na^+$ channels inactivate (a built-in inactivation gate swings shut, even though the activation gate is still open). At the same time, voltage-gated $K^+$ channels, which are slower to respond, finally open. $K^+$ floods out of the cell, pulling the membrane potential back down toward resting levels.

4. Afterhyperpolarization (undershoot): The voltage-gated $K^+$ channels are slow to close, so $K^+$ continues leaving the cell a bit longer than needed. This briefly drives the membrane potential below -70 mV before the channels finally close and the resting potential is restored.

5. Refractory periods limit how quickly a neuron can fire again:

   • Absolute refractory period: The $Na^+$ channel inactivation gates are closed and cannot be reopened regardless of stimulus strength. No second action potential is possible during this window.
   • Relative refractory period: Some $Na^+$ channels have recovered, but $K^+$ channels are still open, making the membrane hyperpolarized. A stronger-than-normal stimulus can trigger another action potential, but a normal stimulus cannot.

Continuous vs. saltatory conduction

Once generated, the action potential needs to travel down the axon to the synaptic terminal. How it gets there depends on whether the axon has a myelin sheath.

Continuous conduction (unmyelinated axons):

• The action potential propagates segment by segment along the entire membrane. Depolarization at one point opens voltage-gated $Na^+$ channels in the adjacent patch, and so on down the line.
• This works, but it's relatively slow because every segment of membrane must go through the full action potential cycle.

Saltatory conduction (myelinated axons):

• The myelin sheath (formed by oligodendrocytes in the CNS or Schwann cells in the PNS) wraps around the axon and acts as an electrical insulator, preventing ion flow through the covered regions.
• Voltage-gated ion channels are concentrated at the nodes of Ranvier, the small gaps between myelin segments.
• The action potential effectively "jumps" from one node to the next. Current generated at one node depolarizes the membrane at the next node, triggering a fresh action potential there.
• This is much faster because the signal skips over the insulated internodes rather than activating every patch of membrane.

Why saltatory conduction matters:

• Speed: Myelinated neurons can conduct signals at up to 120 m/s, compared to roughly 1-2 m/s in small unmyelinated fibers. This is critical for long-distance pathways like those running through the spinal cord.
• Energy efficiency: Fewer ions cross the membrane overall, so the $Na^+/K^+$ pump has less work to do restoring gradients after each impulse.

Synaptic transmission and neurotransmitter release

The action potential's job isn't done until it triggers communication with the next cell. Here's the sequence at a chemical synapse:

1. The action potential arrives at the axon terminal (synaptic knob).
2. Depolarization opens voltage-gated $Ca^{2+}$ channels in the terminal membrane.
3. $Ca^{2+}$ flows into the terminal down its concentration gradient.
4. The rise in intracellular $Ca^{2+}$ causes synaptic vesicles (small membrane sacs loaded with neurotransmitter) to fuse with the presynaptic membrane through a process called exocytosis.
5. Neurotransmitter molecules are released into the synaptic cleft, the narrow gap between the two neurons.
6. Neurotransmitters bind to receptors on the postsynaptic membrane, which can open ion channels or trigger intracellular signaling cascades.

Whether the postsynaptic neuron fires its own action potential depends on its membrane excitability: how close its membrane potential already is to threshold, how many excitatory vs. inhibitory signals it's receiving, and the types of receptors involved. A single synapse rarely triggers an action potential on its own; the postsynaptic neuron typically integrates input from many synapses before reaching threshold.