Work

Activation of Small Conductance Ca2+-Activated K+ Channels Suppresses Electrical and Calcium Alternans in Atrial Myocytes

Year: 2025

Type: article

Abstract: Small conductance Ca2+-activated K+ (SK) channels are expressed in atria and ventricles. However, the data on the contribution of SK channels to atrial action potential (AP) repolarization are inconsistent. We investigated the effect of SK channel modulators on AP morphology in rabbit atrial myocytes and tested the hypothesis that pharmacological activation of SK channels suppresses pacing-induced Ca2+ transient (CaT) and AP duration (APD) alternans. At the cellular level, alternans are observed as beat-to-beat alternations in contraction, APD, and CaT amplitude, representing a risk factor for arrhythmias, including atrial fibrillation. Our results show that SK channel inhibition by apamin did not affect atrial APD under basal conditions. However, SK channel activation by NS309 significantly shortened APD, indicating the expression of functional SK channels. Moreover, the activation of SK channels reduced CaT amplitude and sarcoplasmic reticulum Ca2+ load. Activation of SK channels also suppressed pacing-induced CaT and APD alternans. KV7.1 potassium channel inhibition, simulating long QT syndrome type-1 conditions, increased the risk of atrial CaT alternans, which was abolished by the activation of SK channels. In summary, our data suggest that pharmacological modulation of SK channels can potentially reduce atrial arrhythmia risk arising from pathological APD prolongation.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26083597

Authors: Giedrius Kanaporis, Lothar A. Blatter

Institution: Rush University Medical Center

Language: English

Topic: Cardiac electrophysiology and arrhythmias

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499