Effect of Cl- channel blockers on aconitine-induced arrhythmias in rat heart

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 the AP in a dose-dependent manner with IC50 values of ∼12.3 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. © 2005 The Authors. Journal compilation © 2005 The Physiological Society.