Voltage-dependent channels respond to changes in the transmembrane electric field by rearranging their voltage sensors, triggering increases in selective permeability. The channels reside in three types of conformationally distinct populations: closed states, open states, and a variety of inactivated states. These populations are closely interrelated and, while significant advances have been made in understanding these relationships, their quantitative and molecular description has occupied most of the waking hours of channel biophysicists for the last five decades.
Initial studies of ion channel gating depended on the ability of channels to conduct ions at rates of 106–107 ions/s, allowing for exquisitely sensitive ionic current measurements both at the ensemble and single molecule levels (see Hille, 1992, for references). But, by definition, ionic currents give little or no information on the nonconductive steps of the activation pathway, thus limiting these studies to the transitions to and from the...
