EFFECTS OF RELAXIN ON RAT ATRIAL MYOCYTES .2. INCREASED CALCIUM INFLUX DERIVED FROM ACTION-POTENTIAL PROLONGATION

Relaxin produces positive inotropic and chronotropic effects in rat he arts. The effect of relaxin on the action potential duration (APD) of single quiescent rat atrial cells was investigated with a whole cell p atch clamp. Relaxin induced a significant, dose-dependent prolongation of the APD. This effect was maximal at 200 ng/ml (nominal concentrati on of 33.6 nM), which caused, on average, a 57% increase in the time t aken to reach 90% repolarization. The effect of relaxin was blocked by the protein kinase A inhibitor 5-24 amide, indicating that its effect is mediated by an adenosine 3',5'-cyclic monophosphate-dependent mech anism. The increased APD induced by relaxin caused an enhanced entranc e of calcium, with the charge carried through voltage-activated calciu m channels increased by similar to 25%. This increase was not due to a direct modulation of calcium currents (20); rather, it was a conseque nce of the longer period of cellular depolarization. Our findings that relaxin increased the APD and therefore increased the calcium influx in atrial myocytes could explain the positive inotropic effects induce d by relaxin in atrial preparations.