Wang Teng, Huang Cong-Xin, Jiang Hong, Tang Qi-Zhu, Yang Bo, Li Geng-Shan
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Feb;37(2):102-7.
To investigate the effects of recombinant BmKIM (poly-peptide derived from Asian Scorpion Buthus martensi Karsch) on the sodium current (I(Na)) of isolated ventricular myocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits.
Ventricular myocytes were enzymatically dissociated from adult rabbits. Whole-cell patch-clamp technique was used to record voltage-dependent I(Na). Standard transmembrane action potentials in rabbit hearts in vivo were recorded by using floating glass microelectrodes. Incidence of arrhythmias, the early after depolarization (EAD) and/or delay after depolarization (DAD) were measured in vivo in rabbits post aconitine (100 microg/kg, iv) in the absence or presence of BmKIM (50 microg/kg iv).
(1) BmKIM significantly inhibited I(Na) in a voltage-dependent manner and significantly shifted the I-V curves of I(Na) upward. BmKIM left shifted the inactivation curve of I(Na) and voltages at 50% inactivation of I(Na) were changed from (-70.8 +/- 2.6) mV to (-84.8 +/- 3.5) mV (P < 0.05). BmKIM prolonged the recovery of inactivation of I(Na). In the presence of BmKIM, the time constants of recovery (both tau(f) and tau(s)) of I(Na) were significantly prolonged from (28.9 +/- 6.1) ms and (107 +/- 21.6) ms in control group to (54.2 +/- 7.9) ms (P < 0.05) and (211.1 +/- 34.6) ms (P < 0.01), respectively. (2) BmKIM significantly shortened 50% and 90% of action potential duration (APD(50) and APD(90)), and reduced action potential amplitude (APA), declined maximum up stroke velocity of action potential (V(max)) in vivo. The Q-T duration was shortened and heart rate significantly increased post BmKIM injection. (3) Incidence of aconitine induced ventricular arrhythmias (77.8%) was significantly reduced by BmKIM (22.2%, P < 0.01).
BmKIM significantly blocked I(Na) through affecting the inactivated state of I(Na) in rabbit ventricular myocytes. BmKIM could attenuate the influx of I(Na), therefore shorten action potential duration and reduce action potential amplitude and reduce the incidence of aconitine induced arrhythmias.
研究重组东亚钳蝎毒素BmKIM（一种源自东亚钳蝎的多肽）对兔离体心室肌细胞钠电流（I(Na)）、跨膜动作电位以及乌头碱诱发的体内心律失常的影响。
采用酶解法从成年兔分离心室肌细胞。运用全细胞膜片钳技术记录电压依赖性I(Na)。使用漂浮玻璃微电极记录兔心脏在体的标准跨膜动作电位。在给予或不给予BmKIM（静脉注射50μg/kg）的情况下，测量乌头碱（静脉注射100μg/kg）诱发的兔体内心律失常发生率、早期后除极（EAD）和/或延迟后除极（DAD）。
（1）BmKIM以电压依赖性方式显著抑制I(Na)，并使I(Na)的I-V曲线显著上移。BmKIM使I(Na)的失活曲线左移，I(Na) 50%失活时的电压从（-70.8±2.6）mV变为（-84.8±3.5）mV（P<0.05）。BmKIM延长了I(Na)失活的恢复时间。在BmKIM存在时，I(Na)恢复的时间常数（τf和τs）从对照组的（28.9±6.1）ms和（107±21.6）ms分别显著延长至（54.2±7.9）ms（P<0.05）和（211.1±34.6）ms（P<0.01）。（2）BmKIM显著缩短了动作电位时程的50%和90%（APD(50)和APD(90)），降低了动作电位幅度（APA），降低了在体动作电位最大上升速度（V(max)）。注射BmKIM后，Q-T间期缩短，心率显著增加。（3）BmKIM显著降低了乌头碱诱发的室性心律失常发生率（从77.8%降至22.2%，P<0.01）。
BmKIM通过影响兔心室肌细胞I(Na)的失活状态显著阻断I(Na)。BmKIM可减弱I(Na)内流，从而缩短动作电位时程，降低动作电位幅度，并降低乌头碱诱发的心律失常发生率。
