We investigated the electrophysiological effects of cardiac hypertrophy induced by renal hypertension in rats by comparing transmembrane action potentials (AP) recorded from the papillary muscles of hypertensive (HBP) and normal (SHAM) rats. No significant difference was found between HBP and SHAM AP with regard to resting membrane potential (RMP), action potential amplitude (AMP), overshoot (OS), or maximum rate of rise of the upstroke. In contrast, the duration of 50% (APD50) and 75% (APD75) of repolarization to the RMP was significantly and consistently longer for HBP AP than for SHAM AP. The mechanism for prolonged HBP AP was investigated by changing extracellular fluid composition and by use of ion channel blockers. The responses of HBP and SHAM AP to various treatments differed in a quantitative rather than qualitative fashion. Exposure to C2+-containing or low-Na+Tyrode's solution produced a differentially greater decrease in APD50and APD75 in HBP AP than in SHAM AP. Treatment with D600 also produced differential shortening of HBP AP, but its effect was limited to APD50. In contrast, exposure to Sr2+-containing and TEA-containing Tyrode's solution produced an increase in APD50and APD75, but the lengthening effect was not differentially greater in HBP than in SHAM AP. Treatment with Ca2+-free Tyrode's solution had little effect on APD in either HBP and SHAM rats. None of the treatments had a significant differential action on RMP or AMP in HBP AP as compared to SHAM AP. Our results show that AP prolongation is a specific and consistent feature of hypertrophied myocardium and that the changes responsible for prolonged HBP AP are quantitative rather than qualitative in nature. The specific differential effects of high Ca2+concentration ([Ca2+]o) and low Na+concentration ([Na*]o) on the duration of HBP AP indicate that the membrane sensitivity to these ions is altered in hypertrophied myocardium and that one possible explanation for prolonged HBP AP is slowed inactivation of a Ca2+-inactivated inward current.Circ Res 47: 443-454, 1980