Received July 5, 2005
Revised July 26, 2005
Accepted after revision August 16, 2005
Effect of Cl- channel blockers on aconitine-induced arrhythmias in rat heart
Shi-Sheng Zhou 1*,
Jun Yang 2,
Yao-Qin Li 3,
Lin-Yan Zhao 4,
Ming Xu 2,
Yan-Feng Ding 5
1 Dalian University Medical College
2 Fourth Military Medical University Xi'an
3 Fourth Military Medical University Xi'an 710032, China
4 Dalian University Medical College,
5 Xinxiang Medical College
* To whom correspondence should be addressed. E-mail: zhouss{at}dlu.edu.cn.
 |
Abstract |
|---|
The effects of Cl- channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and niflumic acid (NFA) on aconitine-induced arrhythmias were investigated. Left ventricular pressure and electrocardiogram were monitored in Langendorff-perfused rat hearts. Whole-cell patch-clamp and current-clamp techniques were used to measure sodium current (INa) and action potential (AP) respectively in single rat cardiac ventricular myocytes. Addition of the Na+ channel agonist aconitine (0.1 µM) to the perfusion solution produced polymorphic ventricular arrhythmias with a latent period of 25.5 ± 6.3 s. NPPB could reverse aconitine-induced arrhythmias. A similar effect was observed by using NFA. NPPB and NFA reversibly depressed the upstroke of AP in a dose-dependent manner with IC50 of 
12.3 µM and 73.1 µM, respectively, without significantly affecting the resting potential of rat ventricular myocytes. Both Cl- channel blockers inhibited INa and induced a leftward shift of the steady-state inactivation of INa. In conclusion, the results of this study demonstrate that NPPB as well as NFA can suppress aconitine-induced arrhythmias in rat hearts mainly by inhibiting cardiac INa.
Key Words:
Action potential, Cardiac arrhythmia, Sodium channel
