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Small-conductance calcium-activated potassium current is activated during hypokalemia and masks short-term cardiac memory induced by ventricular pacing

  • Author(s): Chan, YH
  • Tsai, WC
  • Ko, JS
  • Yin, D
  • Chang, PC
  • Rubart, M
  • Weiss, JN
  • Everett, TH
  • Lin, SF
  • Chen, PS
  • et al.
Abstract

© 2015 American Heart Association, Inc. Background - Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKASblockade is proarrhythmic. Methods and Results - Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts; P=0.009). Short-term cardiac memory was assessed by the slope of APD80versus activation time. The slope increased from 0.01 (95% CI, -0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23-0.44) after apamin (P<0.001) during right ventricular pacing and from 0.07 (95% CI, -0.05 to 0.20) to 0.54 (95% CI, 0.06-1.03) after apamin infusion (P=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased IKASin isolated rabbit ventricular myocytes during hypokalemia (P=0.038). Conclusions - Hypokalemia activates IKASto shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKASblockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction.

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