Mechanisms of Action of the KCa2-Negative Modulator AP30663, a Novel Compound in Development for Treatment of Atrial Fibrillation in Man.

ABSTRACT:

Aims

Small conductance Ca²⁺-activated K⁺ channels (SK channels, K_Ca2) are a new target for treatment of atrial fibrillation (AF). AP30663 is a small molecule inhibitor of K_Ca2 channels that is currently in clinical development for treatment of AF. The aim of this study is to present the electrophysiological profile and mechanism of action of AP30663 and its efficacy in prolonging atrial refractoriness in rodents, and by bioinformatic analysis investigate if genetic variants in KCNN2 or KCNN3 influence the expression level of these in human heart tissue.

Methods and results

Whole-cell and inside-out patch-clamp recordings of heterologously expressed K_Ca2 channels revealed that AP30663 inhibits K_Ca

SUBMITTER: Bentzen BH 

PROVIDER: S-EPMC7232560 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature