Effects of BmKIM on sodium current of isolated cardiomyocytes, transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits
10.3760/cma.j.issn.0253-3758.2009.02.003
- VernacularTitle:东亚钳蝎毒素多肽对家兔心室肌细胞钠电流和在体动作电位的影响以及抗心律失常作用研究
- Author:
Teng WANG
1
;
Cong-Xin HUANG
;
Hong JIANG
;
Qi-Zhu TANG
;
Bo YANG
;
Geng-Shan LI
Author Information
1. 武汉大学人民医院
- Keywords:
Anti-arrhythmia agents;
Sodium channels;
Patch-clamp techniques;
Action potentials;
Asian scorpion Buthus martensi Karsch
- From:
Chinese Journal of Cardiology
2009;37(2):102-107
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of recombinant BmKIM (poly-peptide derived from Asian Scorpion Buthus martensi Karsch) on the sodium current (INa) of isolated ventricular myocytes,transmembrane action potential and aconitine induced arrhythmia in vivo in rabbits. Methods Ventricular myocytes were enzymatically dissociated from adult rabbits. Whole-cell patch-clamp technique was used to record voltage-dependent INa. Standard transmembrane action potentials in rabbit hearts in vivo were recorded by using floating glass microelectrodes. Incidence of arrhythmias, the early afterdepolarization (EAD) and/or delay afterdepelarization (DAD) were measured in vivo in rabbits post aconitine (100 μg/kg, iv) in the absence or presence of BmKIM (50 μg/kg iv). Results (1) BmKIM ignificantly inhibited INa, in a voltage-dependent manner and significantly shifted the I - V curves of INa, upward. BmKIM left shifted the inactivation curve of INa, and voltages at 50% inactivation of INa, were changed from (-70. 8±2. 6 ) mV to (-84. 8±3.5 ) mV ( P < 0.05 ). BmKIM prolonged the recovery of inactivation of INa. In the presence of BmKIM, the time constants of recovery ( both τf and τs ) of INa, 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 (APD50 and APD90), and reduced action potential amplitude (APA), declined maximum up stroke velocity of action potential ( Vmax ) in vivo. The Q-T duration was shortened and heart rate significantly increased post BmKIM injection. (3) Incidence of aconitine induced ventrieular arrhythmias (77.8%) was significantly reduced by BmKIM (22.2%, P < 0.01). Conclusions BmKIM significantly blocked INa through affecting the inactivated state of INa in rabbit ventricular myocytes. BmKIM could attenuate the influx of INa, therefore shorten action potential duration and reduce action potential amplitude and reduce the incidence of aconitine induced arrhythmias.
