Jpn. J. Pharmacol. 82 (3), 199-209 (2000)

Protective Effect of Benidipine Against the Abnormal Electrical Activity
in Single Ventricular Myocytes of the Guinea Pig Under Simulated
Ischemic Conditions and Reperfusion

Tomoaki Tokuno1, Katsuhiko Muraki2, Minoru Watanabe2 and Yuji Imaizumi1,*

1Department╩of Pharmacology & Therapeutics and 2Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences,
Nagoya City University, 3-1 Tanabedori, Mizuhoku, Nagoya 467-8603, Japan
*╩To whom all correspondence should be addressed.

Abstract: Induction of electrical abnormalities (EAs) under simulated ischemic conditions and after reperfusion was measured from single cardiac myocytes isolated from guinea pig ventricle using whole-cell voltage or current clamp with perforated patch variation. Conditions of simulated ischemia were produced by the exchange of medium from the standard one oxygenated with 95% O2-5% CO2 gas (pH╩7.4) to the modified one, which contained no glucose, 8╩mM K+ and 30╩mM sodium-d,l-lactate and was gassed with 90% argon-10% CO2 (pH╩6.6). Under the simulated ischemia for 20╩min, EAs such as delayed afterdepolarization, early afterdepolarization, automatic activity or transient inward current were observed in about 37% of myocytes driven electrically at 1╩Hz. Irreversible hypercontracture occurred in myocytes of 10% or less. Upon reperfusion with the standard solution, EAs and hypercontracture were observed in about 43% and 22% of cells, respectively. Glibenclamide-sensitive current was detected during ischemia, but tended to be enhanced during reperfusion. Amplitude of Ca2+ current and ATP-sensitive K+ current after reperfusion varied widely with time and from cell to cell. When myocytes were pretreated for 10╩min with 10╩nM benidipine, a 1,4-dihydropyridine derivative Ca2+ blocker, the incidence of EAs and hypercontracture was markedly reduced, suggesting the protective effect of benidipine against cardiac cell injury during ischemia and reperfusion.

Keywords: Heart, Ischemia, Reperfusion, Electrical abnormality, Benidipine

Copyrightę The Japanese Pharmacological Society 2000

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