Desensitization to the inotropic effect of isoproterenol in cultured ventricular cells

To determine whether monoalyers 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 monoalyers were chronotropically unresponsive to isoproterenol between 10(-9) to 10(-6) M and chronotropically unresponsive to a 6-fold increase in perfusate calcium concentration. However, the cells were very inotropically responsive to calcium and to 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 for isoproterenol was 3 x 10(-9) M. The monolayers rapidly developed dose-dependent desensitization to the inotropic effect of isoproterenol; after a 30-min exposure to 1 x 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 calcium remained unchanged after exposure to 10(-6) M isoproterenol. Thus, the cultured cell preparation shows rapid, sustained, beta receptor specific desensitization to the inotropic effects of a catecholamine.