Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiothoracic Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Heart Rhythm. 2019 Apr;16(4):615-623. doi: 10.1016/j.hrthm.2018.10.033. Epub 2018 Nov 13.
The apamin-sensitive small-conductance calcium-activated K (SK) current I modulates automaticity of the sinus node. I blockade by apamin causes sinus bradycardia.
The purpose of this study was to test the hypothesis that I modulates ventricular automaticity.
We tested the effects of apamin (100 nM) on ventricular escape rhythms in Langendorff-perfused rabbit ventricles with atrioventricular block (protocol 1) and on recorded transmembrane action potential of pseudotendons of superfused right ventricular endocardial preparations (protocol 2).
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 = .006) but accelerated the ventricular escape rate from 51.5 ± 10.7 bpm to 98.2 ± 25.4 bpm (P = .031). Three preparations exhibited bursts of nonsustained ventricular tachycardia and pauses, resulting in repeated burst termination pattern. In protocol 2, apamin increased the ventricular escape rate from 70.2 ± 13.1 bpm to 110.1 ± 2.2 bpm (P = .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 mV/s vs 18.93 ± 3.26 mV/s, N = 3; P = .231, ), but the threshold of phase 0 activation (mV) reduced from -67.97 ± 1.53 to -75.26 ± 0.28 (P = .034). Addition of JTV-519, a ryanodine receptor 2 stabilizer, in 5 preparations reduced escape rate back to baseline.
Contrary to its bradycardic effect in the sinus node, I blockade by apamin accelerates ventricular automaticity and causes repeated nonsustained ventricular tachycardia in normal ventricles. ryanodine receptor 2 blockade reversed the apamin effects on ventricular automaticity.
apamin 敏感的小电导钙激活钾 (SK) 电流 I 调节窦房结的自律性。apamin 阻断可导致窦性心动过缓。
本研究旨在验证 I 调节心室自动性的假说。
我们在 Langendorff 灌流兔心室（房室传导阻滞）中测试了 apamin（100 nM）对心室逸搏节律的影响（方案 1），并在右心室心内膜超流伪腱记录的跨膜动作电位上进行了测试（方案 2）。
所有标本均自发出现心室逸搏节律。在方案 1 中，apamin 将心房率从 186.2 ± 18.0 bpm 降低至 163.8 ± 18.7 bpm（N = 6；P =.006），但将心室逸搏率从 51.5 ± 10.7 bpm 加速至 98.2 ± 25.4 bpm（P =.031）。三个标本表现出非持续室性心动过速和暂停的爆发，导致重复爆发终止模式。在方案 2 中，apamin 将心室逸搏率从 70.2 ± 13.1 bpm 增加至 110.1 ± 2.2 bpm（P =.035）。在 10 个标本中的 6 个标本中，在基础状态下和在 apamin 存在下，从伪腱记录到自发性 4 期去极化。4 期斜率（18.37 ± 3.55 mV/s 与 18.93 ± 3.26 mV/s，N = 3；P =.231）无变化，但 0 期激活的阈值（mV）从-67.97 ± 1.53 降低至-75.26 ± 0.28（P =.034）。在 5 个标本中添加 ryanodine 受体 2 稳定剂 JTV-519，将逸搏率降低回基线。
与窦房结的缓慢性作用相反，apamin 阻断可加速心室自动性，并在正常心室中引起反复非持续室性心动过速。ryanodine 受体 2 阻断逆转了 apamin 对心室自动性的影响。
