Asymmetric Interplay Between K⁺ and Blocker and Atomistic Parameters From Physiological Experiments Quantify K⁺ Channel Blocker Release.

ABSTRACT: Modulating the activity of ion channels by blockers yields information on both the mode of drug action and on the biophysics of ion transport. Here we investigate the interplay between ions in the selectivity filter (SF) of K⁺ channels and the release kinetics of the blocker tetrapropylammonium in the model channel Kcv_NTS. A quantitative expression calculates blocker release rate constants directly from voltage-dependent ion occupation probabilities in the SF. The latter are obtained by a kinetic model of single-channel currents recorded in the absence of the blocker. The resulting model contains only two adjustable parameters of ion-blocker interaction and holds for both symmetric and asymmetric ionic conditions. This data-derived model is corroborated by 3D referenc

SUBMITTER: Gabriel TS 

PROVIDER: S-EPMC8586521 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature