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Mechanism of antiarrhythmic action of verapamil
84 MECHANISM OF ANTIARRHYTHMIC ACTION OF VERAPAMIL. K.Kotaka, Y. Miyazaki, K. Ogawa, T. Dept. of Internal Medicine Faculty of Medicine, Univ.
Satake, S. Sugiyama, T. Ozawa. and Biomedical Chemistry, of Nagoya, Nagoya, Japan.
Antiarrhythmic mechanism of verapamil was investigated. Dogs were divided into 7 groups which were treated with saline, chlorpromazine, chlorpromazine and coenzyme QlO, chlorpromazine and verapamil, lipid, lipid and carnitine, or lipid and verapamil. Administration of chlorpromazine or lipid lowered ventricular multiple response threshold (VMRT) and concomitantly decreased mitochondrial Ca*binding activity. Premeditation with either coenzyme Q10 or carnitine prevented both the lowering of VMRT and the decrease in Ca*-binding activity. Premeditation with verapamil pre ented the lowering of VMRT but not the decrease in CaJ -binding activity. These results suggest that the decrease in mitochondrial Ca*-binding activity is one important arrhythmogenic factor. Verapamil prevents the arrhythmia by blocking Ca*-inward current thus counteracting possible increase in intracellular Ca*, which is derived from impaired Ca*-binding activity.
REVERSIBLE EFFECT OF A HIGH MOLECULAR WEIGHT SULFHYDRYL REAGENT ON ELECTRICALLY STIMULATED BEATING OF MYOCYTES G. Miyakoda, T. Nakamura ISOLATED FROM ADULT RAT HEART. Department of Biology, Faculty of Science, Osaka University, Toyonaka, Osaka and National Cardiovascular Center Research Institute, Suita, Osaka, Japan Isolated myocytes (rod-shaped, quiescent in the pre= sence of 1.5 mM Ca2+) were prepared from adult rat heart. A myocyte suspension was electrically stimulated by field stimulation under microscope by 10 msec pulse of variable and the beating action of myocytes in response voltages, On increasing the pulse voltage, the was recorded. myocyte started to beat at a critical voltage of 5V/cm, and the number of beating cells was maximal at lOV/cm. The beating activity of the myocyte was inhibited by treatment with 100-200 )IM of pCMB-dextran (M-W. 200,000) for 8 min, and the inhibition was reversed by 500 PM DTT. It was suggested that there is SH group(s) in proteins in plasma membrane of the myocyte which is essential for the electrically stimulated beating action, and the function of the SH group(s) is reversibly blocked by the chemical modification from the exterior of the myocyte.
Satake, S. Sugiyama, T. Ozawa. and Biomedical Chemistry, of Nagoya, Nagoya, Japan.
Antiarrhythmic mechanism of verapamil was investigated. Dogs were divided into 7 groups which were treated with saline, chlorpromazine, chlorpromazine and coenzyme QlO, chlorpromazine and verapamil, lipid, lipid and carnitine, or lipid and verapamil. Administration of chlorpromazine or lipid lowered ventricular multiple response threshold (VMRT) and concomitantly decreased mitochondrial Ca*binding activity. Premeditation with either coenzyme Q10 or carnitine prevented both the lowering of VMRT and the decrease in Ca*-binding activity. Premeditation with verapamil pre ented the lowering of VMRT but not the decrease in CaJ -binding activity. These results suggest that the decrease in mitochondrial Ca*-binding activity is one important arrhythmogenic factor. Verapamil prevents the arrhythmia by blocking Ca*-inward current thus counteracting possible increase in intracellular Ca*, which is derived from impaired Ca*-binding activity.
REVERSIBLE EFFECT OF A HIGH MOLECULAR WEIGHT SULFHYDRYL REAGENT ON ELECTRICALLY STIMULATED BEATING OF MYOCYTES G. Miyakoda, T. Nakamura ISOLATED FROM ADULT RAT HEART. Department of Biology, Faculty of Science, Osaka University, Toyonaka, Osaka and National Cardiovascular Center Research Institute, Suita, Osaka, Japan Isolated myocytes (rod-shaped, quiescent in the pre= sence of 1.5 mM Ca2+) were prepared from adult rat heart. A myocyte suspension was electrically stimulated by field stimulation under microscope by 10 msec pulse of variable and the beating action of myocytes in response voltages, On increasing the pulse voltage, the was recorded. myocyte started to beat at a critical voltage of 5V/cm, and the number of beating cells was maximal at lOV/cm. The beating activity of the myocyte was inhibited by treatment with 100-200 )IM of pCMB-dextran (M-W. 200,000) for 8 min, and the inhibition was reversed by 500 PM DTT. It was suggested that there is SH group(s) in proteins in plasma membrane of the myocyte which is essential for the electrically stimulated beating action, and the function of the SH group(s) is reversibly blocked by the chemical modification from the exterior of the myocyte.