title: Trapidil stimulation of slow Ca2+ current in cardiac muscle.
abstract: The effect of trapidil, a coronary vasodilator and positive inotropic agent (associated with elevated tissue cyclic AMP levels due to phosphodiesterase inhibition), was examined on the electrophysiological properties of cardiac muscle. Specifically, the trapidil was tested for its ability to induce slow action potentials (APs), and to affect the maximum upstroke velocity (+Vmax) of the slow APs in the ventricular myocardial cells of isolated perfused chick hearts. The effect of trapidil on the contractions accompanying the slow APs and on the tissue cyclic AMP levels was also examined. 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 hearts could not be excited even by intense electrical stimulation. It was found that trapidil (10(-4)--10(-3) M) induced slow APs accompanied by contractions. Elevation of the trapidil concentration produced dose-dependent increases in +Vmax, dT/dt (first derivative of developed tension) and cyclic AMP. These effects of trapidil were not affected by propranolol, suggesting that they were not mediated by beta-adrenergic receptors. These results support the hypothesis that intracellular cyclic AMP levels regulate the number of available slow channels, thereby controlling contractile force in the heart muscle via the Ca2+ influx mediated by slow channels.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002645:Chickens; D000242:Cyclic AMP / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014192:Trapidil / Q000494:pharmacology*
chemical_list: D011743:Pyrimidines; D000242:Cyclic AMP; D014192:Trapidil; D002118:Calcium