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Neurons typically maintain a resting membrane potential of approximately negative 70 millivolts. This electrical difference across the cell membrane is maintained by the sodium-potassium pump and selective ion permeability. Understanding the resting membrane potential and selective permeability is fundamental to comprehending how neurons generate and transmit electrical signals.

When a neuron depolarizes to threshold, voltage-gated sodium channels open, allowing sodium ions to rush inward down their concentration gradient, rapidly increasing membrane potential to about positive 40 millivolts. Sodium channels then inactivate while voltage-gated potassium channels open more slowly, allowing potassium to flow outward and restore the negative membrane potential.

The refractory period is a brief interval after an action potential when the membrane becomes hyperpolarized, making it nearly impossible for a new action potential to fire. This period prevents the action potential from traveling backward along the axon and ensures signals propagate in one direction only, maintaining the reliability of neural communication.

Myelin, produced by glial cells, insulates axons and prevents current leakage. Voltage-gated channels exist only at nodes of Ranvier, gaps between myelin segments. The action potential regenerates at each node, appearing to jump down the axon in a process called saltatory conduction, enabling rapid transmission over long distances.

When a neuron receives depolarizing signals such as neurotransmitters, its membrane potential becomes more positive. If depolarization reaches threshold potential, voltage-gated sodium channels open, triggering an all-or-none action potential that rapidly propagates along the axon to communicate with other neurons.

Action potentials follow an all-or-none principle because once threshold is reached, positive feedback occurs: sodium influx depolarizes the membrane further, opening more sodium channels. This creates a self-amplifying cascade that either fully triggers an action potential or does not occur at all, ensuring reliable signal transmission.

Squid possess unusually large axons that enabled early electrophysiological studies. In the 1950s, Hodgkin and Huxley used squid giant nerves to record ionic currents and quantitatively describe how sodium and potassium permeability changes generate action potentials, establishing the foundation for modern neurophysiology.