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

Further evidence comes from mutation of the end arginines, especially the most extracellular one, to histidine (54) (55) (56) . In this case, the VSD becomes a proton channel; therefore, the end arginine seems to have the function of preventing the protons that would be moved internally from exiting the VSD; by limiting the proton trajectory, these arginines would leave the protons to produce a . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/371914 doi: bioRxiv preprint capacitative current in response to application of a field, which would produce the same phenomenological result as S4 motion is considered to in the standard models. It has also been shown that mutating the amino acid next to the arginine to histidine does not produce a proton current; the proton is not simply carried across the end of the segment by the histidine moving up or down; if the histidine moved, one would expect such a mutation to provide a current comparable to that of the arginine mutation. The fact that it does not supports the idea that S4 does not move, but the protons do. Much more recently, Zhao and Blunck(57) have shown that the VSD can transport protons (and, to a limited extent, some other cations). Therefore, the idea that protons move through the VSD is not controversial, although the idea that this has to do with gating is. How it is possible to account for the motion of protons in response to voltage while having additional charges move to provide the gating current, in standard models, is not entirely clear. Somehow, the protons would have to not contribute to gating current even when they move.