Voltage-sensor cycle fully described

Abstract

Ion channels provide the most rapid way of communication between the cell interior and the external environment by exploiting the differences in electrolyte composition between the internal and external cellular milieu to transmit electrical and chemical signals (1). Voltage-gated ion channels in particular open and close in response to changes in the membrane electrical potential. Voltage-gated K+ and Na+ channels induce nerve impulses whereas voltage-gated Ca2+ channels initiate muscle contraction and other cellular processes (1). High-resolution X-ray crystallographic structures of some of these proteins have already been determined, showing that they are composed of four subunits, each consisting of six transmembrane segments (S1–S6) and forming two functionally linked, although structurally independent, domains (2⇓–4). The ion conduction pore responsible for selectivity is formed by helices S5 and S6. This pore domain is surrounded by the loosely adherent segments, S1 to S4, which form the voltage sensor. S3 is actually composed of two helices referred as S3a and S3b. S3b forms with S4 a helix–turn–helix called the voltage-sensor paddle (3). The fourth transmembrane helix, S4, is the primary voltage-sensing unit. Four to seven positively charged amino acid spaced at intervals of three in the S4 helix and known as gating charges, and some negatively charged residues distributed in S1, S2, and S3, …