Action potential · Grey Matter

An action potential is the brief, all-or-none reversal of a neuron's membrane voltage that carries a signal along its axon to the next cells, and it is the only output a neuron has.

Action potential. An action potential is the brief, all-or-none reversal of a neuron's membrane voltage that carries a signal along its axon to the next cells, and it is the only output a neuron has.

At rest the inside of a typical neuron sits near −70 mV. Excitatory inputs push it upward; when it crosses a threshold (near −55 mV in the textbook case) voltage-gated sodium channels open, sodium rushes in down its gradient, and the membrane swings to a peak of about +30 mV within a fraction of a millisecond. The sodium channels then inactivate and voltage-gated potassium channels open, potassium leaves, and the voltage falls back, briefly undershooting the resting level before it settles. The whole event lasts about one to two milliseconds.

All or none means the size of the spike does not encode the strength of the input. A stronger input produces more spikes per second, or earlier ones, never a taller spike; information lives in timing and rate.

The refractory period follows each spike: while the sodium channels recover from inactivation the neuron cannot fire again at once, which caps the firing rate and makes the pulse travel in one direction along the axon.

Propagation happens because each patch of depolarised membrane brings the next patch to threshold. Myelin, the fatty wrapping laid by glial cells, lets the spike jump between gaps in the sheath and travel much faster than along a bare axon.

The values are typical. Resting potential, threshold and peak vary by cell type and by the moment; −70, −55 and +30 mV are the reference numbers, and some neurons rest nearer −60 mV.

A line of dominoes is the everyday picture of a spike.

Each one falls only if the one before it falls hard enough, every fall is the same size however hard the push, and a fallen domino has to be stood up again before it can fall a second time.

The ions that move during a spike are few, so the gradients barely change with one spike; restoring them over many spikes is the job of the sodium-potassium pump.

Questions: Does the sodium-potassium pump power each action potential? Only indirectly. The spike runs on gradients that already exist: voltage-gated channels open and sodium and potassium flow down their concentration differences, with no ATP spent during the event itself. The pump works afterwards and continuously, moving three sodium ions out and two potassium ions in per ATP to restore what the spikes let through. One spike changes the concentrations very little, but the brain fires billions of them, and the bill for restoring the gradients after action potentials and synaptic currents is the largest item in its energy budget. How does a spike arriving at a terminal turn into released transmitter? The spike depolarises the terminal and opens voltage-gated calcium channels clustered at the release sites. Calcium enters and binds synaptotagmin on vesicles that the SNARE proteins (synaptobrevin on the vesicle, syntaxin and SNAP-25 on the terminal) have already half-zipped to the membrane. The calcium-bound synaptotagmin lets the zipping finish, the two membranes fuse and the vesicle empties into the cleft, all in well under a millisecond. Blocking the calcium channels blocks release, which is how calcium was shown to be the link. How long does a spike take to cross the brain or reach a foot? It depends on the fibre. The fastest myelinated motor and muscle-sense fibres conduct at about 80 to 120 m/s, so a command covering a metre to the foot takes around 10 ms; thin unmyelinated pain fibres at about 1 m/s need a second for the same distance, which is why a burn is felt after the first sharp prick. Inside the brain most axons are short and slower, and a signal between hemispheres through the corpus callosum takes from a few to a few tens of milliseconds, depending on the fibre. Synaptic delays at each relay add to the conduction time. How does a Neuropixels probe tell which neuron fired? Inside the tissue, a recording site a few tens of micrometres from a neuron picks up that neuron's action potential directly, as a sharp dip of a fraction of a millisecond. The probe's 960 sites are packed so closely along its shank that each spike appears on several neighbouring sites with a characteristic pattern of sizes and shapes. Spike-sorting software groups spikes by that footprint, and each group is taken to be one neuron, which turns 384 channels of voltage into the firing times of hundreds of individual cells. How do potassium channels end each spike and decide how fast a neuron can fire? Voltage-gated potassium channels open a little after the sodium channels, as the spike rises, and the potassium leaving the cell pulls the voltage back down while the sodium channels inactivate. Fast-closing types end the spike quickly and let the cell recover within a millisecond or two, which is how fast-spiking interneurons sustain hundreds of spikes per second. Slower potassium currents, some activated by the calcium that enters with each spike, build up during a train and produce a lasting afterhyperpolarisation, so the cell slows down (adaptation). Which potassium channels a neuron expresses is therefore a large part of its firing personality. What happens to a neuron's membrane between −70 mV and +30 mV? Inputs nudge the resting voltage of about −70 mV upward until it reaches threshold, near −55 mV, where voltage-gated sodium channels open together. Sodium floods in and the inside swings positive to about +30 mV in a fraction of a millisecond. The sodium channels then inactivate and potassium channels open, so potassium leaves and the voltage drops back, briefly below rest. The whole cycle takes one to two milliseconds, and the spike is always the same size: a stronger input changes how often the neuron fires, never how high. Why does a neuron either fire a full spike or none at all? Voltage-gated sodium channels open when the membrane depolarises, and the sodium they let in depolarises it further, which opens more of them. Below threshold, potassium leaking out wins and the voltage drifts back; once enough sodium channels open that the inward current outruns the outward one, the feedback runs away and the membrane swings to its peak. The size of the spike is then set by the sodium gradient and the number of channels, never by the size of the input that crossed threshold. This positive feedback was first described quantitatively by Hodgkin and Huxley in the squid giant axon. Why does myelin make white matter conduct signals so much faster? An action potential on a bare axon has to regenerate itself on every patch of membrane, which is slow (around 0.5 to 2 m/s). Myelin wraps the axon in many layers of insulating membrane, leaving short gaps, the nodes of Ranvier, where the sodium channels are concentrated; current flows passively under the insulation and the spike is regenerated only at the nodes, so it appears to jump from node to node. Large myelinated axons reach tens of metres per second, up to about 120 m/s, which is what lets distant brain regions exchange signals within milliseconds.