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

There is also a cavity in the pore in which an ion is found in the X-ray structure. An incoming potassium ion would have to interact with such an ion, which could knock back an incoming ion that moved beyond the entrance to the pore toward the cavity. This ion has no particular force pushing it into the gate; there is a concentration dependence of the free energy of the ion in the external solution(102) (see Fig. 3 ) that suggests a free energy gradient on K + that might help somewhat, especially with getting the ion into the . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 gate. We have done a limited calculation of the interaction potential that suggests that the water so substantially reduces the interaction energy between an ion at the gate and the cavity ion that, as long as the ion at the gate stays at the gate, the repulsion energy is almost zero. However, the ion then cannot advance, or displace the water or the ion in the cavity. Therefore, we proposed that the gate would have to oscillate, complexing and holding the incoming ion, which then cannot be knocked back, so that the ion in the cavity would proceed to the bottom state of the selectivity filter, given a little time, once the bottom state of the selectivity filter becomes available. Once the cavity cleared, the ion at the gate could move into the cavity, not so much having pushed the previous ion forward, as having simply allowed it to move, and then replaced it. The cycle is indicated in Fig. 9 , reproduced from (40) . This implies that the gate can complex K + well enough to force the ion in the cavity to move up, or at least allow it to move up. The complex must not be so tight that, once the cavity becomes available, it cannot release the K + ; the cavity location is then of lower energy than the solution, so that the ion moves into the cavity rather than back to solution, and the current continues. Here it is interesting to compare the KcsA closed structure to the K v 1.2 open structure, for both of which X-ray structures exist. Kariev and Green noted that the gate opening was about a 3 Ã… increase in the radius of the intracellular gate (167) . 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 appears to be an increased density of water at the gate, rather than a change in protein conformation or gate diameter. Adapted from ref. (40) Then the 15 Ã… N -N distance (between nitrogens of two prolines from opposite VSDs in K v 1.2) would be consistent with the entrance of a hydrated K + , with the ion not yet complexed by protein. A calculation of the pore region, with a total of 50 water molecules in a total of 870 atoms showed that there was no difference in the N-N distance with a K + at the gate, but about three more water molecules clustered there, for a total of thirteen, compared to about ten when the ion was just below the selectivity filter.