COEXISTENCE OF FUNCTIONING BETA(1)-ADRENOCEPTOR AND BETA(2)-ADRENOCEPTOR IN SINGLE MYOCYTES FROM HUMAN VENTRICLE

Background. Both beta1- and beta2-adrenoceptors (beta1AR and beta2AR) are present in human ventricle. This study was designed to determine whether the two subtypes contribute to contraction in single myocytes from human heart. Methods and Results. (-)-Epinephrine increased the contraction amplitude and velocity of single myocytes isolated from the ventricles of failing and nonfailing human hearts. Concentration-response curves to (-)-epinephrine were constructed in the presence and absence of selective antagonists for beta1AR (CGP 20712A) and beta2AR (ICI 118,551). Responses to (-)-epinephrine were antagonized to a variable degree by the blockers, suggesting heterogeneous contribution of beta1AR and beta2AR among cells. The most common response in single myocytes was that ICI 118,551 (50 nmol/L) shifted the concentration-response curve less than 10-fold: this was lower than the 100-fold shift expected for a pure beta2AR effect. Inclusion of CGP 20712A (300 nmol/L) with ICI 118,551 shifted the (-)-epinephrine curve still further. These observations suggest that both beta1AR and beta2AR contribute to the increase in contraction amplitude with (-)-epinephrine in this group of myocytes. When 300 nmol/L CGP 20712A was present as the sole antagonist, only a marginal shift of the concentration-response curve for (-)-epinephrine was usually observed, indicating that beta1AR were not mediating the effect of these low concentrations of (-)-epinephrine. Both beta1AR and beta2AR mediated a considerable abbreviation of the time to peak contraction and time to 50% relaxation in the single cells. Conclusions. beta1AR and beta2AR coexist and function on human ventricular myocytes. At low (-)-epinephrine concentrations, contractile responses are predominantly mediated by beta2AR rather than beta1AR in myocytes from failing hearts.