Exploring K _v 1.2 Channel Inactivation Through MD Simulations and Network Analysis.

ABSTRACT: The KCNA2 gene encodes the K _v 1.2 channel, a mammalian Shaker-like voltage-gated K⁺ channel, whose defections are linked to neuronal deficiency and childhood epilepsy. Despite the important role in the kinetic behavior of the channel, the inactivation remained hereby elusive. Here, we studied the K _v 1.2 inactivation via a combined simulation/network theoretical approach that revealed two distinct pathways coupling the Voltage Sensor Domain and the Pore Domain to the Selectivity Filter. Additionally, we mutated some residues implicated in these paths and we explained microscopically their function in the inactivation mechanism by computing a contact map. Interestingly, some pathological residues shown to impair the inactivation lay on

SUBMITTER: Costa F 

PROVIDER: S-EPMC8721119 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature