Reduction of I-Ca,I-L and I(to1)density in hypertrophied right ventricular cells by simulated high altitude in adult rats

The present paper describes the effect of a simulated hypobaric condition (at the altitude of 4500 m) on morphological characteristics and on some ionic currents in ventricular cells of adult rats. According to current data, chronic high-altitude exposure led to mild right ventricular hypertrophy. Increase in right ventricular weight appeared to be due wholly or partly to an enlargement of myocytes. The whole-cell patch-clamp technique was used and this confirmed, by cell capacitance measurement, that chronic high-altitude exposure induced an increase in the size of the right Ventricular cells. Hypertrophied cells showed prolongation of action potential (AP). Four ionic currents, playing a role along with many others in the precise balance of inward and outward currents that control the duration of cardiac AP, were investigated. We report a significant decrease in the transient outward (I-to1) and in the L-type calcium current (I-CaL) densities while there was no significant difference in the delayed rectifier current (I-K) or in the inward rectifier current (I-Kl) densities in hypertrophied right ventricular cells compared to control cells. At a given potential the decrease in I-to1 density was relatively more important than the decrease in I-CaL density. In both cell types, all the currents displayed the same voltage dependence. The inactivation kinetics of I-to1 and I-CaL or the steady-state activation and inactivation relationships were not significantly modified by chronic high-altitude exposure. We conclude that chronic high-altitude exposure induced true right ventricular myocyte hypertrophy and that the decrease ih I-to1 density might account for the lengthened action potential, or have a partial effect. (C) 1997 Academic Press Limited.