An action potential (often mistakenly called an “axon potential” because it travels along the axon) is a brief electrical impulse that nerve cells use to send signals from one end to the other. It lasts roughly one to two milliseconds, involves a rapid voltage swing of about 100 millivolts, and moves in only one direction along the nerve fiber. Every sensation you feel, every movement you make, and every thought you form depends on billions of these tiny electrical spikes firing in coordinated patterns throughout your nervous system. The process is more intricate than a simple on-off switch, though, and the details matter for understanding everything from anesthesia to neurological disease.
The Starting Voltage
Before an action potential can fire, a neuron has to be in a particular electrical state. A resting nerve cell sits at roughly −70 millivolts relative to its surroundings, a difference called the resting potential. That negative charge exists because the cell membrane carefully controls which ions sit where. Sodium ions are concentrated outside the cell, potassium ions are concentrated inside, and a protein pump embedded in the membrane actively maintains those gradients by pushing sodium out and potassium in.1PubMed. On the concept of resting potential–pumping ratio of the Na⁺/K⁺ pump and concentration ratios of potassium ions outside and inside the cell to sodium ions inside and outside the cell The membrane at rest is far more permeable to potassium than to sodium, so potassium ions leak outward and leave a net negative charge behind. This resting voltage is the loaded spring that makes everything else possible.
Where the Spike Begins
Not every part of a neuron is equally good at launching an action potential. The trigger zone is a small stretch of axon right where it leaves the cell body, called the axon initial segment. This region is packed with an unusually high density of voltage-sensitive ion channels, making it far more excitable than the surrounding membrane.2PubMed Central. Axon initial segments: structure, function, and disease When incoming signals from other neurons push the voltage at this spot past a critical threshold (around −55 millivolts in many neurons), the action potential ignites.
The Voltage Spike and Its Reset
Once threshold is reached, the action potential unfolds in two rapid phases. In the rising phase, voltage-gated sodium channels snap open, letting sodium ions flood into the cell. Sodium channels are the first to respond to voltage changes, and the inward rush of positive ions drives the interior voltage sharply upward, often overshooting past zero to about +30 or +40 millivolts.3PubMed Central. Physiology, Sodium Channels This rising phase is extremely fast because it feeds on itself: sodium entry makes the inside more positive, which opens more sodium channels, which lets in more sodium.
The voltage does not stay high for long. Within a fraction of a millisecond, the sodium channels automatically inactivate, meaning a built-in gate swings shut and stops sodium flow regardless of what the voltage is doing. At about the same time, slower-acting potassium channels open. Potassium ions pour out of the cell, carrying positive charge with them and dragging the voltage back down. Different types of potassium channels contribute to this falling phase and help determine how quickly the cell resets.4PubMed. Different voltage-dependent potassium conductances regulate action potential repolarization and excitability in frog myelinated axon The voltage typically dips slightly below the resting level (a brief undershoot) before the sodium-potassium pump restores the original ion balance.
The Cooldown Period
Immediately after firing, a neuron cannot fire again right away. This enforced pause is the refractory period, and it comes in two flavors. During the absolute refractory period, no stimulus, no matter how strong, can trigger another spike. In human muscle fibers, this window has been measured at roughly two to five milliseconds, depending on the fiber type.5Electroencephalography and Clinical Neurophysiology. Refractory period of human muscle after the passage of a propagated action potential That window exists because the sodium channels are still inactivated and physically cannot reopen yet. After that comes the relative refractory period, when a new action potential is possible but requires a stronger-than-normal stimulus. The refractory period serves a critical purpose: it ensures the action potential travels forward along the axon rather than bouncing backward, because the membrane behind the spike is temporarily unable to fire.
How the Signal Travels
An action potential does not simply appear at one spot and vanish. It propagates down the full length of the axon like a lit fuse, each patch of membrane triggering the next. In unmyelinated axons (those without insulation), this happens continuously: sodium entry at one point depolarizes the adjacent membrane enough to open its channels, and the wave creeps forward step by step. This is relatively slow.
Most of the long-distance axons in your body, however, are wrapped in myelin, a fatty insulating sheath produced by specialized support cells. Myelin dramatically changes the game. The insulation prevents ion flow across most of the membrane, but at regular gaps called nodes of Ranvier, the axon is exposed and loaded with sodium channels. The action potential effectively jumps from one node to the next, a process called saltatory conduction.6PubMed Central. Saltatory Conduction along Myelinated Axons Involves a Periaxonal Nanocircuit Recent work has refined this classic picture by showing that a thin conducting fluid layer between the axon and the myelin sheath plays a role in how voltage spreads between nodes, producing gradually attenuating waves under the myelin that help drive the next node’s response.7Cell. A Submyelin Conductance Pathway Underlies Rapid Saltatory Conduction in Myelinated Axons – Section: Submyelin Resistance Produces Saltatory Conduction in the Temporal Domain The practical result is that saltatory conduction is much faster and more energy-efficient than continuous conduction, since ions need to cross the membrane only at the nodes.
What Determines Speed
Action potentials in the human body travel at wildly different speeds depending on where they are. Large, thickly myelinated motor fibers can conduct at around 80 to 120 meters per second, fast enough that the delay between deciding to move your hand and the signal reaching your fingers is barely perceptible. Thin, unmyelinated pain fibers, by contrast, conduct at about 0.5 to 2 meters per second, which is why a stubbed toe registers a sharp initial jolt (carried by faster fibers) followed by a slower, throbbing ache.
The main factors governing speed are axon diameter and myelin thickness. Conduction velocity in myelinated fibers is roughly proportional to diameter, and for a given axon diameter, adding myelin makes things faster up to an optimal ratio of axon diameter to total fiber diameter.8PubMed. Determinants of conduction velocity in myelinated nerve fibers Work on the primate pyramidal tract (the main pathway for voluntary movement) has shown that about half of the axons there are smaller than one micrometer in diameter, with some so thin they were previously undetectable with standard microscopy. Those small fibers conduct at well under 18 meters per second.9PubMed Central. Axon diameters and conduction velocities in the macaque pyramidal tract The nervous system, in other words, does not optimize for raw speed everywhere. Some pathways need precision and timing coordination more than they need to be fast.
What Happens When the Signal Arrives
The whole point of sending an action potential down an axon is to do something at the other end. When the spike reaches the axon terminal, it opens voltage-gated calcium channels. Calcium rushes in, and within a few hundred microseconds, it triggers the release of chemical messengers called neurotransmitters into the gap between the nerve cell and its target.10PubMed Central. Calcium control of neurotransmitter release At a neuromuscular junction, for example, a single action potential can release hundreds of packets of transmitter molecules, which cross the gap and activate receptors on the muscle fiber to initiate contraction.11PubMed. Presynaptic calcium influx, neurotransmitter release, and neuromuscular disease The electrical signal has been converted to a chemical one, allowing information to jump from cell to cell.
The Energy Bill
Running the nervous system is metabolically expensive, and a big part of that cost comes from action potentials. Every spike lets sodium in and potassium out, and the sodium-potassium pump has to burn ATP (the cell’s energy currency) to shove those ions back where they belong. Estimates place the cost of a single action potential at roughly a million molecules of ATP at a single node of Ranvier alone, scaling up by orders of magnitude when you account for the full membrane area of larger neurons.12PubMed. The cost of an action potential Your brain, which accounts for about 2 percent of your body weight, consumes around 20 percent of your resting energy, and much of that goes to keeping neurons electrically ready and restoring ion gradients after firing. Myelination helps here too: by restricting ion flow to the nodes, it drastically cuts the total number of ions that need to be pumped back, making myelinated signaling far cheaper per meter of axon.
When Things Go Wrong
Because action potentials depend on a precise arrangement of ion channels and myelin, disruption at either level can cause serious disease.
In multiple sclerosis (MS), the immune system attacks myelin. When segments of myelin are stripped away, the exposed axon can no longer conduct action potentials efficiently. The result is conduction block or dramatic slowing, and the body tries to compensate by redistributing sodium channels along the now-bare membrane. If the demyelination persists, that compensatory rearrangement eventually fails, and the axon itself degenerates.13PubMed Central. Demyelination in multiple sclerosis Even mild, patchy demyelination can introduce timing jitter into individual spikes, and that jitter accumulates over long axons, broadening the compound electrical signal that clinicians measure on nerve conduction studies.14PubMed Central. Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach Symptoms like limb weakness, numbness, and vision problems in MS map directly to which axon tracts have lost their insulation.
The ion channels themselves can also be the problem. Mutations in genes encoding voltage-gated sodium channels can alter how the channel opens, closes, or recovers, leading to a range of disorders grouped under the term channelopathies. In the brain, these mutations are a significant cause of epilepsy, where neurons fire uncontrollably.15PubMed Central. Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review In skeletal muscle, similar mutations can produce periodic paralysis or myotonia (involuntary muscle stiffness). The range of possible symptoms is broad because sodium channels exist in many subtypes throughout the body, and a mutation’s effect depends on which subtype is affected and how.16PubMed Central. Sodium channelopathies of skeletal muscle and brain
Poisons, Medicines, and Sodium Channels
The critical role of sodium channels in generating action potentials makes them a prime target for both natural toxins and pharmaceutical drugs. Tetrodotoxin, found in pufferfish, and saxitoxin, produced by certain marine algae, both plug the pore of sodium channels and block ion flow entirely. A dose large enough to shut down the sodium channels in the nerves controlling breathing is lethal. Research on these toxins has been instrumental in revealing how sodium channels work at the molecular level.17PubMed Central. Neurotoxins and their binding areas on voltage-gated sodium channels
Medicine takes the same principle and dials it down. Local anesthetics like lidocaine work by partially blocking sodium channels in sensory nerves, preventing action potentials from reaching the brain and eliminating pain without affecting consciousness. Anticonvulsant drugs used in epilepsy often target sodium channels too, stabilizing them in an inactivated state so that neurons are less likely to fire rapid bursts. Antiarrhythmic drugs for the heart follow a similar logic, since cardiac muscle cells also rely on sodium-channel-driven action potentials to coordinate heartbeat rhythm.18PubMed Central. Shellfish toxins targeting voltage-gated sodium channels
How Scientists First Figured This Out
Much of what we know about action potentials traces back to work done in the late 1940s and early 1950s by Alan Hodgkin and Andrew Huxley, who studied the giant axon of the squid. That axon, about a millimeter in diameter, was large enough to insert an electrode inside. Using a technique called voltage clamping, they held the membrane at a fixed voltage and measured the ion currents flowing across it, which let them work out the behavior of sodium and potassium channels without the confounding effects of the voltage changing as they measured.19PubMed Central. A brief historical perspective: Hodgkin and Huxley The mathematical model they built from those measurements predicted the shape, speed, and threshold of the action potential with remarkable accuracy and earned them a Nobel Prize in 1963. Nearly every detail in this article rests on a foundation they laid.
Sodium Channels Before Nervous Systems
Voltage-gated sodium channels are so central to nerve function that you might assume they evolved alongside neurons. They did not. Sodium channels appear to have evolved from calcium channels, and homologs of modern sodium channel genes have been found in choanoflagellates, single-celled organisms that are the closest living relatives of animals.20PubMed Central. Adaptive evolution of voltage-gated sodium channels: the first 800 million years Even more striking, the placozoa, one of the simplest animals on Earth with no nervous system whatsoever, possess expressed sodium channel genes.21PubMed Central. Evolution of sodium channels predates the origin of nervous systems in animals The ancestral channels were probably permeable to both sodium and calcium, and full sodium selectivity developed later. This means the molecular toolkit for electrical signaling was already in place before neurons existed, and evolution repurposed it rather than building it from scratch.
Talking Without Synapses
The standard story of neural communication is that an action potential travels down the axon, triggers neurotransmitter release, and the chemical signal crosses a synapse to reach the next cell. But there is a lesser-known alternative: ephaptic coupling. When axons run close together, the electrical field generated by an action potential in one fiber can directly influence the voltage in a neighboring fiber, without any chemical intermediary. Modeling studies show that when two axons are packed tightly enough, their action potentials can attract or repel each other in time, eventually locking into synchronized firing patterns.22PubMed Central. A mathematical model of ephaptic interactions in neuronal fiber pathways: Could there be more than transmission along the tracts?
This is not just theoretical. In the cerebellum, Purkinje cells are arranged in dense rows, and experiments have shown that when one Purkinje cell fires an action potential, the resulting extracellular voltage change near its axon initial segment is large enough to open sodium channels in its neighbor, promoting synchronized firing between the two cells.23Neuron. Rapid Synchronization of Cerebellar Purkinje Cells through Ephaptic Coupling Ephaptic coupling may play a role in the precise timing required for motor coordination and other brain functions, adding a layer of complexity beyond what synapse-only models predict.
Controlling Action Potentials with Light
One of the most powerful tools in modern neuroscience is optogenetics, a technique that allows researchers to trigger or silence action potentials in specific neurons using pulses of light. The approach typically involves inserting a gene for a light-sensitive ion channel, such as channelrhodopsin-2, into target neurons. When blue light hits these modified channels, they open and allow positive ions in, pushing the neuron past threshold and producing an action potential with millisecond precision. Researchers have used this method in brain slices to fire individual Purkinje cell axons on command and record the downstream effects on connected neurons.24PubMed Central. Optimizing Optogenetic Activation of Purkinje Cell Axons to Investigate the Purkinje Cell – DCN Synapse
The technique extends beyond the brain. By delivering channelrhodopsin genes to specific motor neuron pools through injection into a muscle and relying on the virus to travel backward along the axon, researchers have achieved optogenetic control of individual muscles in freely moving animals. A small optical fiber cuff around the nerve delivers light and selectively activates just those axons carrying the light-sensitive channel.25PLoS ONE. Optogenetic Control of Targeted Peripheral Axons in Freely Moving Animals The potential clinical applications include more precise prosthetic limb control, targeted pain management, and therapies for movement disorders, all built on the ability to command a single axon’s action potentials with a flash of light.