Potassium channels are responsible for the selective permeation of K+ ions across cell membranes.  McKinnon received the Nobel Prize for crystallizing the KcsA channel and structurally resolving the selectivity filter that passes K+ ions but not Na+ and other similarly sized ions. The mechanism involved both water and K+ ions passing, one after the other, through the filter.  That conclusion has recently been called into question with a new mechanism that lacks water and suggests that hard-sphere ion collisions are necessary for conduction. Moreover, the new mechanism appears to explain almost all existing experimental data equally as well as the original mechanism. We have addressed this conundrum using 2D IR spectroscopy of a semisynthetic KcsA channel with site-specific <sup>13</sup>C<sup>18</sup>O isotope labels in the selectivity filter. The ultrafast time-resolution of 2D IR spectroscopy provides an instantaneous snapshot of the multi-ion configurations and structural distributions that occur spontaneously in the filter. Two elongated features are resolved, revealing the statistical weighting of two ion configurations. We study these configurations of a function of the structural state of the seletivity filter and the gate, comparing the experimental data to molecular dynamics simulations of each of the proposed methods. The results provide a clear picture of ion occupancy, testing the models, and expanding upon the role of gating in the mechanism of potassium ion conductance.

A potassium channel conundrum addressed with 2D IR spectroscopy

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.