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Effect of Cl − channel blockers on aconitine‐induced arrhythmias in rat heart
Author(s) -
Zhou ShiSheng,
Yang Jun,
Li YaoQin,
Zhao LinYan,
Xu Ming,
Ding YanFeng
Publication year - 2005
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2005.031484
Subject(s) - aconitine , niflumic acid , chemistry , sodium channel , channel blocker , agonist , patch clamp , purkinje fibers , perfusion , pharmacology , cardiology , medicine , electrophysiology , sodium , anesthesia , receptor , biochemistry , chromatography , organic chemistry , calcium
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 μ m ) 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 IC 50 values of ∼12.3 and ∼73.1 μ m , 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 .