Role of alpha1-adrenoceptor subtypes in production of the positive inotropic effects in mammalian myocardium: implications for the alpha1-adrenoceptor subtype distribution.

Both alpha1A- and alpha1B-adrenoceptor subtypes are present in mammalian myocardium. Alpha1-adrenoceptor activation can enhance myocardial contractility, and two possible inotropic mechanisms are proposed: an increase in myofilament Ca2+ sensitivity and an increase in transsarcolemmal Ca2+ influx during action potential prolongation that accompanies the transient outward current inhibition. We suggest that the former is mediated by the alpha1B-adrenoceptor subtype and the latter is by the alpha1A-adrenoceptor subtype. The alpha1B-adrenoceptor subtype may be located on a space more proximal to the sympathetic nerve endings than the alpha1A-adrenoceptor subtype, because the positive inotropic effect of endogenous norepinephrine was mediated entirely by the alpha1B-adrenoceptor subtype. In some species, the sustained positive inotropic effect develops following the transient negative inotropic effect, which is mediated by the alpha1A-adrenoceptor subtype.