Inactivation of the Kv2.1 channel through electromechanical coupling.

ABSTRACT: The Kv2.1 voltage-activated potassium (Kv) channel is a prominent delayed-rectifier Kv channel in the mammalian central nervous system, where its mechanisms of activation and inactivation are critical for regulating intrinsic neuronal excitability^1,2. Here we present structures of the Kv2.1 channel in a lipid environment using cryo-electron microscopy to provide a framework for exploring its functional mechanisms and how mutations causing epileptic encephalopathies^3-7 alter channel activity. By studying a series of disease-causing mutations, we identified one that illuminates a hydrophobic coupling nexus near the internal end of the pore that is critical for inactivation. Both functional and structural studies reveal that inactivation in Kv2.1 results from dynamic alt

SUBMITTER: Fernandez-Marino AI 

PROVIDER: S-EPMC10567553 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature