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 Imaizumi^1,*


¹Departmentﾊof Pharmacology & Therapeutics and ²Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences,
Nagoya City University, 3-1 Tanabedori, Mizuhoku, Nagoya 467-8603, Japan
*ﾊ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ﾊ7.4) to the modified one, which contained no glucose, 8ﾊmM K⁺ and 30ﾊmM sodium-d,l-lactate and was gassed with 90% argon-10% CO₂ (pHﾊ6.6). Under the simulated ischemia for 20ﾊ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ﾊ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ﾊmin with 10ﾊ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