The four “charged particles” predicted to underlie the voltage-dependent gating of some ion channels (Hodgkin and Huxley, 1952) are now known to be the four S4 segments, putative α-helices in which every third residue (in many, but not all, S4 segments) is either arginine or lysine. These charged structures must reside at least partly within the membrane electric field and move some of their positive charges across this electric field in response to changes of membrane potential. There are several classes of movement that could accomplish this feat (for some examples, see Yellen, 1998), including a collapse of the electric field around the S4 segment, a novel mechanism suggested in a paper in this issue of the Journal of General Physiology (Bell et al., 2004).
The electrophoretic task of the voltage sensor is to move charge down a gradient of...
