The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as Shown by Quantum Calculations

Alisher M Kariev; Michael E Green

The arginines are assumed to be positively charged (the solution pK a is close to 12) , so taking the motion of these charges to constitute the gating current was a natural assumption. Our proposed gating mechanism does not fit in the group of standard models, since it does not have the S4 TM helix providing the gating current by a large scale movement with its putatively positive arginines. We show that the arginines need not always be charged in the membrane context; a proton from the arginine can transfer to a neighboring glutamate. This is one step in a proton current that would be detected as gating current, although the total charge displacement is actually the gating current, and is not limited to movement of specific charged entities. No such proton transfer is contemplated in any standard model. We provide quantum calculations as part of the evidence to support this proton transfer. The VSDs for the various channels that belong to this family are not all alike. The H v 1 channel is, in its entirety, a close analog of the VSD; it is a proton channel. Its structure, to a reasonable approximation, is that of a dimer of a VSD of a potassium channel, especially at the extracellular end. Some other channels appear to have proton transmission sections that are also analogous, although they are not as closely related as H v 1; some are listed in a later section. to affect gating (22) . The pore section is in the center.