Evaluation of four KCNMA1 channelopathy variants on BK channel current under Ca_V1.2 activation.

ABSTRACT: Variants in KCNMA1, encoding the voltage- and calcium-activated K⁺ (BK) channel, are associated with human neurological disease. The effects of gain-of-function (GOF) and loss-of-function (LOF) variants have been predominantly studied on BK channel currents evoked under steady-state voltage and Ca²⁺ conditions. However, in their physiological context, BK channels exist in partnership with voltage-gated Ca²⁺ channels and respond to dynamic changes in intracellular Ca²⁺ (Ca²⁺_i). In this study, an L-type voltage-gated Ca²⁺ channel present in the brain, Ca_V1.2, was co-expressed with wild type and mutant BK channels containing GOF (D434G, N999S) and LOF (H444Q, D965V) patient-associated variants in HE

SUBMITTER: Dinsdale RL 

PROVIDER: S-EPMC11370921 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature