Work

NaV1.5 or KCa2 channel blockade does not increase arrhythmia risk in hypokalemic rabbit hearts, unlike KV11.1 inhibition with dofetilide

Year: 2025

Type: article

Abstract: Aims The small conductance calcium activated potassium channel ( KCNN1-3 ; K Ca 2.1–3) is recognized as a possible new anti-arrhythmic drug target for treatment of atrial fibrillation (AF). The aim of this study is to investigate potential ventricular effects of K Ca 2 channel inhibition under normal, bradycardic and hypokalemic conditions and compare these to classical class I and III anti-arrhythmic drugs. Methods and results Rabbit hearts were isolated, AV-ablated, mounted in an ex vivo Langendorff preparation and perfused with normokalemic (4 mM K + ) Krebs-Henseleit solution, followed by perfusion with drug (AP14145 3 µM; AP30663 1.5 µM; dofetilide 10 nM; flecainide 1.5 µM) or vehicle control. The perfusion was then changed to hypokalemic solution (2.5 mM K + ) in presence of drug. Changes in ventricular action potential duration were assessed by monophasic action potential recordings. Neither of the K Ca 2 channel inhibitors (AP14145 or AP30663) or flecainide (Na V 1.5 inhibitor) prolonged ventricular action potential duration (APD90) or increased pro-arrhythmic markers, whereas dofetilide (K V 11.1 blocker) prolonged APD and increased the susceptibility to ventricular arrhythmia. Conclusions These findings suggests that K Ca 2 channels have minimal importance for ventricular repolarization in healthy rabbit hearts under both normo- and hypokalemic conditions.

Source: IJC Heart & Vasculature

DOI: 10.1016/j.ijcha.2025.101699