Gating currents indicate complex gating of voltage-gated proton channels

Abstract

The voltage-gated proton channel (HV1) is a unique molecule that resides at the interface between ion channels and bioenergetic molecules that use proton gradients to store or transduce energy. HV1 plays key roles in the health and disease of diverse tissues and species (1). Important information regarding the physical components of ion-channel gating (opening and closing, which in turn activate or terminate flow of ionic current through the pore) can be obtained by measuring the size, kinetics, and voltage dependence of gating currents. Fig. 1 illustrates different mechanisms by which gating currents might be generated. In their landmark voltage-clamp studies of sodium and potassium channels in squid axons in the mid-20th century, Hodgkin and Huxley (2) deduced that ( i ) ionic current flowed through discreet sites (channels) in the membrane; ( ii ) these permeation pathways were gated, opening and closing in response to changes in membrane potential; and ( iii ) this process most likely involved the movement of charged groups across part or all of the transmembrane electric field. They recognized that the movement of charges within the electric field should generate a small capacitive current, but it was smaller than they could detect. The predicted gating currents were measured in sodium channels two decades later (3⇓⇓–6). Sodium-channel gating currents were ∼300 times smaller than the ionic current and were mostly over in 1 ms (3). Several properties of proton channels frustrated attempts to measure their gating currents until recently. Carmona et al. (7) report gating currents in HV1 from the sea squirt Ciona intestinalis . A contemporaneous study by De La Rosa and Ramsey (8) reports gating currents in human HV1. The clever experimental approaches devised by these groups to overcome the intransigence of HV1 and their conclusions … [↵][1]1Email: tdecours{at}rush.edu. [1]: #xref-corresp-1-1