Effect of Cl- channel blockers on aconitine-induced arrhythmias in rat heart.
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 (I(Na)) and action potential (AP), respectively, in single rat cardiac ventricular myocytes. Addition of the Na+ channel agonist aconitine (0.1 microM) 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 the AP in a dose-dependent manner with IC50 values of approximately 12.3 and approximately 73.1 microM, respectively, without significantly affecting the resting potential of rat ventricular myocytes. Both Cl- channel blockers inhibited I(Na) and induced a leftward shift of the steady-state inactivation of I(Na). 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 I(Na).
Zhou
Shi-Sheng
SS
Institute of Basic Medical Sciences, Medical College, Dalian University, Dalian 116622, China. zhouss@dlu.edu.cn
Yang
Jun
J
Li
Yao-Qin
YQ
Zhao
Lin-Yan
LY
Xu
Ming
M
Ding
Yan-Feng
YF
D000157:Aconitine; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D009544:Niflumic Acid / Q000627:therapeutic use*; D009579:Nitrobenzoates / Q000627:therapeutic use*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects
D018118:Chloride Channels; D009579:Nitrobenzoates; D015222:Sodium Channels; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D009544:Niflumic Acid; D000157:Aconitine