An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG.

ABSTRACT:

Background

Cyclic Nucleotide-Binding Domain (CNBD)-family channels display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, the human Ether-a-go-go Related Gene (hERG) channel and the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel share high amino acid sequence similarity and identical domain structures. hERG conducts outward current and is activated by positive membrane potentials (depolarization), whereas HCN conducts inward current and is activated by negative membrane potentials (hyperpolarization). The structural basis for the "opposite" voltage-sensing properties of hERG and HCN remains unknown.

Results

We found the voltage-sensing domain (VSD) involves in modulating the gating polarity of hERG. We

SUBMITTER: Liu Z 

PROVIDER: S-EPMC11380439 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature