Voltage-gated ion channels

Abstract

Electrical signaling by ion channels is a fundamental cellular regulatory pathway in all organisms from prokaryotes to humans. Voltage-gated Na+ (VGSC), Ca2+ (VGCC), and K+ (VGPC) channels are responsible for action potential generation in electrically excitable cells, for example, neurons and muscle cells, and for regulation of membrane potential and intracellular Ca2+ levels in other cell types. The basic functional properties of this protein family were initially defined in classic voltage-clamp studies by Hodgkin and Huxley in 1952. During the 1970s, many scientists built upon the fundamental insights of these pioneers to investigate electrical signal transduction using patch-clamp techniques, to measure ion channel function by neurotoxin-activated ion flux, and to detect VGSC proteins (the first member of this family to be studied biochemically) by high affinity binding of the neurotoxins tetrodotoxin, saxitoxin, and scorpion toxin (discussed later in this chapter). However, the molecular basis of excitability remained unclear until the 1980s, when Dr. William A. Catterall and his colleagues at the University ofWashington discovered the VGSC protein (in 1980) and the VGCC protein (in 1984).