voltagegated

Voltage-gated ion channels are transmembrane proteins that open or close in response to changes in membrane potential. They are essential for electrical signaling in neurons, muscle cells, and other excitable tissues. Unlike ligand-gated channels, voltage-gated channels respond to voltage across the cell membrane to control ion flow.

Most voltage-gated channels share a common architecture: a pore-forming domain that selects for specific ions, and one or more voltage-sensing domains containing positively charged residues in the S4 segment. Upon depolarization, the voltage sensor moves, triggering opening of the pore and ion conductance. Many channels also exhibit inactivation, a temporary cessation of current despite continued depolarization, often via an intracellular inactivation gate.

The main families are voltage-gated sodium (Nav), potassium (Kv), and calcium (Cav) channels. Nav channels initiate and propagate action potentials; Kv channels repolarize the membrane and shape action potentials; Cav channels couple electrical activity to processes like Ca2+-triggered exocytosis. Structurally, Nav and Cav channels have four homologous domains (I–IV) each with six transmembrane segments; Kv channels have four subunits, each with six segments, forming a tetramer.

Pharmacological agents include tetrodotoxin (Nav blockade), lidocaine, dihydropyridines (Cav L-type), and tetraethylammonium (Kv). Mutations in voltage-gated channels cause channelopathies such as epilepsies, periodic paralysis, and long QT syndrome. Voltage-gated channels are ancient and diverse, fundamental to cellular excitability, and serve as major drug and toxin targets in medicine.