The two most important ions in the transmission of action potentials are Na⁺ and potassium K⁺. Voltage-gated Na⁺ channels have three types of states: deactivated (closed), activated (open), and inactivated (closed). During excitation of the cell, Na⁺ channels are activated through removal of an intracellular “activation gate,” and Na⁺ begins flowing into the cell. Once some Na⁺ ion channels begin opening, the voltage drops further, causing more channels to open until the membrane depolarizes. Na⁺ channels are more sensitive to voltage change than K⁺ channels are and open more rapidly. Thus in a depolarization, the Na⁺ ions will rush into the cell faster than the K⁺ ions move outward. This sudden depolarization, called an action potential, will briefly result in a +30 millivolt potential difference. Once the slowly-opening voltage-gated K⁺ ion channels have opened and allowed K⁺ to flow out, the action potential is ended. Once Na⁺ channels are activated, they quickly are inactivated due to an “inactivation gate” that blocks the inside of the channel shortly after it has been activated. During an action potential, the channel remains inactivated for a few milliseconds after depolarization. The inactivation is removed when the membrane potential of the cell repolarizes after the falling phase of the action potential. This allows the channels to be activated again during the next action potential. Thus the Na⁺ ion channels initiate the action potential, and the K⁺ ion channels terminate it. The channels then close, and the sodium pump can restore the resting potential of −70 millivolts.

Membrane polarity is also affected by ligand-gated channels that open when neurotransmitters, the ligands of synaptic transmission, bind to specific receptors connected to the channels. Glutamate is the primary excitatory neurotransmitter and gamma-aminobutyric acid (GABA), the principal inhibitory transmitter. Synaptic transmission is mediated by glutamate that is released from the pyramidal neurons and depolarizes and excites the target neurons via ionotropic receptors (NMDA, α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid [AMPA], and kainic acid [KA]). Glutamate channel opening allows Na⁺ and Ca²⁺ to enter the cell, resulting in depolarization, whereas with GABA channel opening, Cl⁻ enters the cell, resulting in hyperpolarization.

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