Structural Mechanism of ω-Currents in a Mutated Kv7.2 Voltage Sensor Domain from Molecular Dynamics Simulations.

ABSTRACT: Activation of voltage-gated ion channels is regulated by conformational changes of the voltage sensor domains (VSDs), four water- and ion-impermeable modules peripheral to the central, permeable pore domain. Anomalous currents, defined as ω-currents, have been recorded in response to mutations of residues on the VSD S4 helix and associated with ion fluxes through the VSDs. In humans, gene defects in the potassium channel Kv7.2 result in a broad range of epileptic disorders, from benign neonatal seizures to severe epileptic encephalopathies. Experimental evidence suggests that the R207Q mutation in S4, associated with peripheral nerve hyperexcitability, induces ω-currents at depolarized potentials, but the fine structural details are still elusive. In this work, we use atom-detailed molecul

SUBMITTER: Alberini G 

PROVIDER: S-EPMC8023575 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature