Resting state structure of the hyperdepolarization activated two-pore channel 3.

ABSTRACT: Voltage-gated ion channels endow membranes with excitability and the means to propagate action potentials that form the basis of all neuronal signaling. We determined the structure of a voltage-gated sodium channel, two-pore channel 3 (TPC3), which generates ultralong action potentials. TPC3 is distinguished by activation only at extreme membrane depolarization (V₅₀ ∼ +75 mV), in contrast to other TPCs and Na_V channels that activate between -20 and 0 mV. We present electrophysiological evidence that TPC3 voltage activation depends only on voltage sensing domain 2 (VSD2) and that each of the three gating arginines in VSD2 reduces the activation threshold. The structure presents a chemical basis for sodium selectivity, and a constricted gate suggests a closed pore consi

SUBMITTER: Dickinson MS 

PROVIDER: S-EPMC6995003 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature