Reduction of ICa,Land Ito1Density in Hypertrophied Right Ventricular Cells by Simulated High Altitude in Adult Rats

Abstract

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 (Ito1) and in thel-type calcium current (ICa,L) densities while there was no significant difference in the delayed rectifier current (IK) or in the inward rectifier current (IK1) densities in hypertrophied right ventricular cells compared to control cells. At a given potential the decrease in Ito1density was relatively more important than the decrease in ICa,Ldensity. In both cell types, all the currents displayed the same voltage dependence. The inactivation kinetics of Ito1and ICa,Lor 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 in Ito1density might account for the lengthened action potential, or have a partial effect.