Studies on Heart. XX. Further Effects of Bovine Ventricle Protein (BVP) and Antiarrhythmic Peptide (AAP) on Myocardial Cells in Culture

Abstract

In order to elucidate the physiological significance of bovine ventricle protein (BVP) and antiarrhythmic peptide (AAP) obtained from bovine heart, we investigated their effects on spreading, beating, arrhythmic movements, macromolecular synthesis, continuous cultivation and calcium incorporation of cultured rat myocardial cells in Eagle's minimum essential medium (MEM) supplemented with or without serum. Both BVP and AAP at 10−7m stimulated the spreading phenomenon and the protein synthesis of myocardial cells in serum-free culture, and promoted prolonged survival with spontaneous beating in culture with 1% serum. As regards the beating properties of myocardial cells, they had different effects. AAP, which improved the arrhythmic movements induced by low potaasium, high calcium or addition of ouabain, depressed the beating rate and the ratio of beating cells at 10−7–10−6m. However, BVP promoted beating even in continuous cultivation over 10 days, but did not affect the arrhythmic movements induced by low potassium or high calcium at 10−7–10−6m. When myocardial cells were cultured in modified Eagle's MEM-0.5% bovine serum albumin at 0.5 mm potassium, 5 mM calcium or 0.2 mM ouabain (which induced arrhythmic movements of cultured cells), their spreading was significantly suppressed. Quinidine, oxytocin and insulin, which improve arrhythmia in the intact heart, stimulated the spreading phenomena and improved the arrhythmic movements induced by low potassium as well as AAP. AAP also decreased the incorporation of 45Ca into myocardial cells, but BVP did not have this effect. It is concluded that AAP shows antiarrhythmic action as a result of depressions of calcium incorporation and potassium effusion, with low excitation and prolonged survival of myocardial cells. BVP shows prolonged survival with spontaneous and strong beating in continuous culture for 10 days. © 1980, The Pharmaceutical Society of Japan. All rights reserved.