Facilitation of I _Kr current by some hERG channel blockers suppresses early afterdepolarizations.

ABSTRACT: Drug-induced block of the cardiac rapid delayed rectifying potassium current (I _Kr), carried by the human ether-a-go-go-related gene (hERG) channel, is the most common cause of acquired long QT syndrome. Indeed, some, but not all, drugs that block hERG channels cause fatal cardiac arrhythmias. However, there is no clear method to distinguish between drugs that cause deadly arrhythmias and those that are clinically safe. Here we propose a mechanism that could explain why certain clinically used hERG blockers are less proarrhythmic than others. We demonstrate that several drugs that block hERG channels, but have favorable cardiac safety profiles, also evoke another effect; they facilitate the hERG current amplitude in response to low-voltage depolarization. To investigate h

SUBMITTER: Furutani K 

PROVIDER: S-EPMC6363420 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature