Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing.
Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing.
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DOI：
10.1161/circulationaha.114.015125
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发表时间：
2015-10-13
期刊：
影响因子：
37.8
通讯作者：
Chen PS
中科院分区：
文献类型：
--
作者：
Chan YH;Tsai WC;Ko JS;Yin D;Chang PC;Rubart M;Weiss JN;Everett TH 4th;Lin SF;Chen PS
低钾血症增加心室颤动（VF）的易感性。我们假设阿帕胺敏感的小电导钙激活钾电流（IKAS）在低钾血症期间被激活，并且IKAS阻断是心律失常的。在正常血钾血症或低血钾血症期间，对23只经Langendorff灌注的兔心室进行房室传导阻滞和右心室（RV）或左心室（LV）起搏的光学定位。Apamin延长动作电位持续时间（APD）至80%复极（APD80）在正常血钾时延长26 ms[95%置信区间，CI, 14-37]，在低血钾时延长54 ms [CI， 40 - 68] （P=0.01）。在低钾血症心室，APD恢复的最大斜率、APD交替的PCL阈值、波破诱导的PCL和空间不一致APD交替的面积增加。Apamin显著促进持续VF的诱导（从3/9个心脏到9/9个心脏，P=0.009）。通过APD80随激活时间的斜率评估短期心脏记忆。左室起搏时，apamin输注后斜率从基线时的0.01 [CI,−0.09 ~ 0.12]增加到0.34 [CI, 0.23 ~ 0.44] (P<0.001)；左室起搏时，apamin输注后斜率从0.07 [CI,−0.05 ~ 0.20]增加到0.54 [CI, 0.06 ~ 1.03] （P=0.045）。膜片钳研究证实低钾血症期间IKASin分离兔心室肌细胞增加（P=0.038）。低钾血症激活IKAS以缩短APD并维持心室起搏后期激活位点的复极储备。IKAS阻断显著延长了后期激活位点的APD，促进了VF的诱导。
Hypokalemia increases the vulnerability to ventricular fibrillation (VF). We hypothesize that the apamin-sensitive small conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. Optical mapping was performed in 23 Langendorff perfused rabbit ventricles with atrioventricular block and either right ventricular (RV) or left ventricular (LV) pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 ms [95% confidence interval, CI, 14–37] during normokalemia and by 54 ms [CI, 40 to 68] during hypokalemia (P=0.01) at 1000 ms pacing cycle length (PCL). In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the PCL threshold of APD alternans, the PCL for wavebreak induction and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained VF (from 3/9 hearts to 9/9 hearts, P=0.009). Short term cardiac memory was assessed by the slope of APD80 versus activation time. The slope increased from 0.01 [CI, −0.09 to 0.12] at baseline to 0.34 [CI, 0.23 to 0.44] after apamin (P<0.001) during RV pacing, and from 0.07 [CI, −0.05 to 0.20] to 0.54 [CI, 0.06 to 1.03] after apamin infusion (P=0.045) during LV pacing. Patch-clamp studies confirmed increased IKASin isolated rabbit ventricular myocytes during hypokalemia (P=0.038). Hypokalemia activates IKAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKAS blockade prominently lengthens the APD at late activation sites and facilitates VF induction.