biostudies-literatureKanaporis GNHLBI NIH HHSNational Institutes of HealthNIH HHS51-67https://www.ebi.ac.uk/biostudies/studies/S-EPMC9878619biostudies-literatureUnknown601(1)At the cellular level, cardiac alternans is observed as beat-to-beat alternations in contraction strength, action potential (AP) morphology and Ca²⁺ transient (CaT) amplitude, and is a risk factor for cardiac arrhythmia. The (patho)physiological roles of small conductance Ca²⁺ -activated K⁺ (SK) channels in ventricles are poorly understood. We tested the hypothesis that in single rabbit ventricular myocytes pharmacological modulation of SK channels plays a causative role for the development of pacing-induced CaT and AP duration (APD) alternans. SK channel blockers (apamin, UCL1684) had only a minor effect on AP repolarization. However, SK channel activation by NS309 resulted in significant APD shortening, demonstrating that functional SK channels are well eThe Journal of physiologyActivation of small conductance Ca²⁺ -activated K⁺ channels suppresses Ca²⁺ transient and action potential alternans in ventricular myocytes.PMC9878619HL134781HL057832R01 HL132871R01 HL057832R01 HL164453HL132871R01 HL155762R01 HL134781HL155762HL164453Kanaporis GBlatter LAfalseActivation of small conductance Ca²⁺ -activated K⁺ channels suppresses Ca²⁺ transient and action potential alternans in ventricular myocytes.At the cellular level, cardiac alternans is observed as beat-to-beat alternations in contraction strength, action potential (AP) morphology and Ca²⁺ transient (CaT) amplitude, and is a risk factor for cardiac arrhythmia. The (patho)physiological roles of small conductance Ca²⁺ -activated K⁺ (SK) channels in ventricles are poorly understood. We tested the hypothesis that in single rabbit ventricular myocytes pharmacological modulation of SK channels plays a causative role for the development of pacing-induced CaT and AP duration (APD) alternans. SK channel blockers (apamin, UCL1684) had only a minor effect on AP repolarization. However, SK channel activation by NS309 resulted in significant APD shortening, demonstrating that functional SK channels are well e2023-01-01T00:00:00Z2023 Jan2025-04-26T07:48:10.035Z2025-04-06T12:29:44.846ZS-EPMC98786193642654810.1113/jp28387010.1113/JP283870