 Solution

A typical voltage-gated potassium channel has four subunits, each with six membrane-spanning segments. S1–S4 form a voltage-sensing domain; S5–S6 and their intervening loop form the pore and selectivity filter. Conserved positively charged side chains along S4 move through part of the membrane electric field when the voltage changes. Countercharges and hydrated crevices in the surrounding sensor help make this movement possible. Coupling between the sensor and pore, including the S4–S5 region and S6 gate, changes the probability of opening. A voltage-gated sodium channel usually combines four related domains in one large protein, rather than four identical independent proteins.

The evidence separates charge movement, structural arrangement and functional coupling. A transient ion-channel gating current can persist when permeating ionic electric current is suppressed: some charged parts of the channel itself move. Comparing integrated ion-channel gating charge with channel opening tests their coupling. Charge-neutralization experiments change both total moved charge and voltage dependence, implicating S4 basic residues and countercharges elsewhere; they do not show that S4 alone supplies every charge. ^[ref]

Crystal structure of a mammalian voltage-dependent Shaker family K+ channel by Stephen B. Long and others supplies structural evidence for the arrangement. Voltage-dependent accessibility and optical reports of sensor motion provide complementary functional tests. No one static structure is a movie of gating, and a perturbation that abolishes current can disrupt folding or pore function rather than selectively remove voltage sensing. Agreement between structural, electrical and motion-sensitive measurements supports the mechanism more strongly than any one observation alone.