Interplay between inotropic and lusitropic effects of cyclic adenosine monophosphate on the myocardial cell

beta-Adrenergic agonists and other agents that increase cellular levels of cyclic adenosine monophosphate (cyclic AMP) exert complex actions on myocardial cell function that enhance both the force of contraction and the rate of relaxation. At the same time that cyclic AMP increases the amount of activator Ca2+ released at the onset of systole, which increases contractility, this intracellular messenger accelerates the removal of activator Ca2+ from the cytosol by the sarcoplasmic reticulum, which promotes relaxation. Cyclic AMP also increases Ca2+ sensitivity of the sarcoplasmic reticular Ca2+ pump and desensitizes contractile proteins to Ca2+, both of which favor relaxation. Thus, the lusitropic effects of cyclic AMP, which allow the heart to remove increased amounts of activator Ca2+ from the cytosol, occur simultaneously with cyclic AMP's inotropic effects. This interplay between inotropic and lusitropic effects allows beta-adrenergic agonists to increase myocardial contractility while accelerating relaxation, a combination of effects that allows the ventricles to fill during the agonist-induced tachycardia.