Cyclic adenosine monophosphate modulation of contractility via slow Ca2+ channels in chick heart

The catecholamines exert a positive inotropic effect associated with elevated tissue cyclic AMP levels and possibly with increase in the number of membrane slow cationic channels available for voltage activation. In the present study, catecholamines (isoproterenol, dopamine and dobutamine) were tested for their ability to affect the maximum upstroke velocity (+ V_max) of the slow action potentials, the first derivative ($\text{d}\text{T}\text{d}\text{t}$) of developed tension accompanying the slow responses, and the tissue cyclic AMP levels in the ventricular myocardium of isolated perfused chick hearts. To study the slow channels exclusively, the fast Na⁺ channels were voltage inactivated by elevated (25 mm) K⁺. In this condition of functional removal of the fast channels, the heart could not be excited by intense electrical stimulation. It was found that these catecholamines induced slow action potentials accompanied by contractions. Elevation of the concentration of these agents produced increases in + V_max, $\text{d}\text{T}\text{d}\text{t}$, and cyclic AMP in a dose-dependent fashion; a close correlation was obtained between the cyclic AMP level, + V_max and $\text{d}\text{T}\text{d}\text{t}$. These results support the hypothesis that the increases in + V_max of the slow action potentials and in contraction are explained by increase in the number of available slow channels mediated by intracellular cyclic AMP levels, and the resulting increase in the Ca²⁺ influx.