Neurons communicate by firing action potentials—the electrochemical signal that is propagated along the axon. The signal results in the release of neurotransmitters at axon terminals, thereby transmitting information to the nervous system. An action potential is a specific "all-or-none" change in membrane potential that results in a rapid spike in voltage.

Membrane potential in neurons

Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they receive signals—for instance, from neurotransmitters or sensory stimuli—their membrane potential can hyperpolarize (become more negative) or depolarize (become more positive), depending on the nature of the stimulus.

If the membrane becomes depolarized to a specific threshold potential, voltage-gated sodium (Na⁺) channels open in response. Na⁺ has a higher concentration outside of the cell as compared to the inside, so it rushes in when the channels open, moving down its electrochemical gradient. As positive charge flows in, the membrane potential becomes even more depolarized, in turn opening more channels. As a result, the membrane potential quickly rises to a peak of around +40 mV.

At the peak of the action potential, several factors drive the potential back down. The influx of Na⁺ slows because the Na⁺ channels start to inactivate. As the inside of the cell becomes more positive, there is less electrical attraction driving Na⁺ inwards. The initial depolarization also triggers the opening of voltage-gated potassium (K⁺) channels, but they open more slowly than the Na⁺ channels. Once these K⁺ channels open—around the peak of the action potential—K⁺ rushes out down its electrochemical gradient. The reduced influx of positive charge from Na⁺ combined with the efflux of positive charge from K⁺ rapidly lowers the membrane potential.

For a brief period after an action potential, the membrane is hyperpolarized compared to the resting potential. This is called the refractory period because, during this time, the cell is incapable of producing a new action potential, thus preventing the action potential from moving backward in a cell.

Myelin sheath increases conductivity

Specialized glial cells—oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS)—extend long processes that wrap around neuronal axons. This wrapping provides insulation, preventing leakage of the current as it travels along the axon. Additionally, electrical signals are propagated down myelinated axons by passive, positive current flow in the myelinated regions. Voltage-gated Na⁺and K⁺ channels are only found in the gaps between the myelin at the nodes of Ranvier, triggering regeneration of the action potential at each node. In this way, the action potential appears to "jump" down the axon at the nodes—a process called saltatory conduction.

The giant nerves of the squid

John Z. Young, a zoologist, and neurophysiologist, discovered that the squid has nerve cells with axons much wider than mammalian neurons. These nerves control a rapid escape maneuver that is facilitated by the faster action potentials that are only possible in the larger axons. The larger diameter of the axons enabled the initial studies and descriptions of the ionic mechanisms involved in an action potential. This work was pioneered in the 1950s by Alan Hodgkin and Andrew Huxley while working on the giant nerve of the Atlantic squid. Together, they described the permeability of axonal membranes to sodium and potassium ions and were able to quantitatively reconstruct the action potential based on their electrode recordings.