Non-sedating antihistamines block G-protein-gated inwardly rectifying K⁺ channels.

ABSTRACT:

Background and purpose

A second-generation antihistamine, terfenadine, is known to induce arrhythmia by blocking hERG channels. In this study, we have shown that terfenadine also inhibits the activity of G-protein-gated inwardly rectifying K⁺ (GIRK) channels, which regulate the excitability of neurons and cardiomyocytes. To clarify the underlying mechanism(s), we examined the effects of several antihistamines on GIRK channels and identified the structural determinant for the inhibition.

Experimental approach

Electrophysiological recordings were made in Xenopus oocytes and rat atrial myocytes to analyse the effects of antihistamines on various GIRK subunits (K_ir 3.x). Mutagenesis analyses identified the residues critical for inhibition by terfenadine and

SUBMITTER: Chen IS 

PROVIDER: S-EPMC6692640 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature