DESENSITIZATION TO THE INOTROPIC EFFECT OF ISOPROTERENOL IN CULTURED VENTRICULAR CELLS

Abstract

To determine whether monolayers of cultured chick embryo ventricular cells would show tachyphylaxis to chronotropic and inotropic effects of a .beta.-adrenergic agonist, spontaneously contracting monolayers of primary cell cultures were studied using a phase-contrast microscope-video motion detector system that permitted quantitation of the chronotropic and inotropic state. The monolayers were chronotropically unresponsive to isoproterenol between 10-9-10-6 M and chronotropically unresponsive to a 6-fold increase in perfusate Ca concentration. The cells were very inotropically responsive to Ca and isoproterenol. Expressing the isoproterenol inotropic response as a percentage of response to 3.6 mM Ca, the response to 10-6 M isoproterenol was 79 .+-. 4% of the Ca response and the EC50 [median effective concentration] for isoproterenol was 3 .times. 10-9 M. The monolayers rapidly developed dose-dependent desensitization to the inotropic effect of isoproterenol; after a 30-min exposure to 1 .times. 10-6 M isoproterenol, the inotropic response was 40 .+-. 5% of the initial response; desensitization was long-lasting and could be prevented by propranolol. Response to Ca remained unchanged after exposure to 10-6 M isoproterenol. Thus, the cultured cell preparation shows rapid, sustained, .beta.-receptor-specific desensitization to the inotorpic effects of a catecholamine.