Pulmonary artery hypertension causes the right ventricle (RV) to become hypertrophied and fail. During this process the RV undergoes electrophysiological remodeling with resultant changes in action potential duration (APD). This study evaluated the effects of removing intracellular calcium (thus preventing forward-mode sodium-calcium exchanger (NCX) current) on the altered APD restitution in hypertrophied RV rat myocytes. Additionally experiments were performed using ranolazine to assess the effects of the late sodium current (INa,late) on APD restitution in these cells. Male Wistar rats were given a single i.p. injection of monocrotaline (60 mg/kg) or an equivalent volume of saline. When clinical symptoms of heart failure became apparent (3-4 weeks later) animals were euthanized and the hearts excised. RV myocytes were enzymatically isolated and used for measurements of APD at pacing rates between 1 and 9 Hz. Both sham and failing cells were either left untreated, loaded with BAPTA-AM (5 µM for 15 min), or perfused with 5 µM ranolazine. Some cells treated with BAPTA were also used under discontinuous (4 kHz) action potential (AP) clamp to impose the AP recorded at 1 Hz at pacing rates of 1, 2, 5 and 7 Hz. Myocytes from the failing RV had a steeper APD90 restitution curve and significantly longer APD between 1 and 9 Hz compared to sham cells at all pacing rates (p < 0.01 – 0.0001, 2 Way ANOVA, Tukeys post-test, n = 5-6 cells). Despite this greater APD shortening, under AP clamp, compensation currents in failing myocytes were smaller in amplitude as pacing frequency increased (at 7 Hz, p < 0.05 – 0.0001 at -40 to 0 mV, n = 5-7). However, integrating the currents showed that in failing cells (which had a longer APD), greater positive charge was passed (p < 0.05 – 0.0001 at -40 to -25 mV, n = 3-7). Failing RV cells that were preloaded with BAPTA had no significant change in APD90. However, at APD25, BAPTA increased the gradient of the restitution curve causing significant increases in duration at slower pacing frequencies (p < 0.05 – 0.001 at 1-2 Hz, n = 5 cells). Under AP clamp, BAPTA caused increases in positive charge passed at more positive membrane potentials, compared to untreated hypertrophied cells. Inhibition of INa,late using 5 µM ranolazine had no effect on either the APD90 or APD25 in either sham or failing RV myocytes (n = 6-9). These data show that cells isolated from the monocrotaline treated RV have a longer APD and steeper APD restitution than those from sham animals. Additionally, our results suggest that steeper APD restitution in failing RV myocytes is not caused by either forward mode NCX or INa,late. Steeper restitution with decreased currents recorded under AP clamp is consistent with an increase in membrane resistance in failing cells. This may be caused by downregulation of K+ currents. We are currently investigating this possibility.