BK channels of five different subunit combinations underlie the de novo KCNMA1 G375R channelopathy.

ABSTRACT: The molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the tetrameric BK channel is unknown. Here, we address this question by recording from single BK channels expressed to mimic a G375R mutation heterozygous with a WT allele. Five different types of functional BK channels were expressed: 3% were consistent with WT, 12% with homotetrameric mutant, and 85% with three different types of hybrid (heterotetrameric) channels assembled from both mutant and WT subunits. All channel types except WT showed a marked gain-of-function in voltage activation and a smaller decrease-of-function in single-channel conductance, with both changes in function becoming more pronounced as the number of mutant subunits per tetrameric channel increased. T

SUBMITTER: Geng Y 

PROVIDER: S-EPMC10067970 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature