Wan, JuyiChen, MuWang, ZhuoEverett, Thomas H., IVRubart-von der Lohe, MichaelShen, ChangyuQu, ZhilinWeiss, James N.Boyden, Penelope A.Chen, Peng-Sheng2018-12-052018-12-052018Wan, J., Chen, M., Wang, Z., Everett, T. H., Rubart-von der Lohe, M., Shen, C., … Chen, P.-S. (2018). The Small Conductance Calcium Activated Potassium Current Modulates the Ventricular Escape Rhythm in Normal Rabbit Hearts. Heart Rhythm. https://doi.org/10.1016/j.hrthm.2018.10.033https://hdl.handle.net/1805/17909Background The apamin-sensitive small-conductance calcium-activated K (SK) current (IKAS) modulates automaticity of the sinus node; IKAS blockade by apamin causes sinus bradycardia. Objective To test the hypothesis that IKAS modulates ventricular automaticity. Methods We tested the effects of apamin (100 nM) on ventricular escape rhythms in Langendorff perfused rabbit ventricles with atrioventricular (AV) block (Protocol 1) and on recorded transmembrane action potential (TMP) of pseudotendons of superfused right ventricular (RV) endocardial preparations (Protocol 2). Results All preparations exhibited spontaneous ventricular escape rhythms. In Protocol 1, apamin decreased the atrial rate from 186.2±18.0 bpm to 163.8±18.7 bpm (N=6, p=0.006) but accelerated the ventricular escape rate from 51.5±10.7 to 98.2±25.4 bpm (p=0.031). Three preparations exhibited bursts of nonsustained ventricular tachycardia (NSVT) and pauses, resulting in repeated burst-termination pattern. In Protocol 2, apamin increased the ventricular escape rate from 70.2±13.1 to 110.1±2.2 bpm (p=0.035). Spontaneous phase 4 depolarization was recorded from the pseudotendons in 6 of 10 preparations at baseline and in 3 in the presence of apamin. There were no changes of phase 4 slope (18.37±3.55 vs. 18.93±3.26 mV/s, p=0.231, N=3), but the threshold of phase 0 activation (mV) reduced from -67.97±1.53 to -75.26±0.28 (p=0.034). Addition of JTV-519, a ryanodine receptor 2 (RyR2) stabilizer, in 5 preparations reduced escape rate back to baseline. Conclusions Contrary to its bradycardic effect in the sinus node, IKAS blockade by apamin accelerates ventricular automaticity and causes repeated NSVT in normal ventricles. RyR2 blockade reversed the apamin effects on ventricular automaticity.enPublisher Policyautomaticitycalcium clockidioventricular rhythmArticle