IONIC BASIS OF ACTION-POTENTIAL PROLONGATION OF HYPERTROPHIED CARDIAC MYOCYTES ISOLATED FROM HYPERTENSIVE RATS OF DIFFERENT AGES

Objective: The aim was to determine the ionic basis of action potential lengthening associated with cardiac hypertrophy. Methods: Action potentials and ionic currents of left ventricular myocytes isolated from normal and hypertrophied hearts were recorded with patch pipettes. Since cardiac hypertrophy is a time dependent process, myocytes isolated from hearts of spontaneously hypertensive rats (SHR) of different ages (3 and 18 months old) were compared with those of age matched normotensive controls (Wistar Kyoto rats, WKY). Results: Membrane capacitance, an index of cell size, was significantly higher in SHR than WKY. The degree of action potential prolongation was independently correlated with hypertension and its duration, resulting in a statistically significant lengthening of action potential in 18 month old SHR compared to age matched WKY and to 3 month old SHR. I-Ca,I-L density was not significantly modified in hypertrophied myocytes compared to normal controls. Depolarising steps positive to -40 mV activated an outward current, which was composed of both transient (I-to) and maintained components (I-late) and played a major role in controlling repolarisation in rat ventricular myocytes. I-Kl density was significantly reduced in SHR myocytes compared to age matched WKY and was also smaller in 18 month old compared to 3 month old SHR. I-late was not statistically different in 3 and 18 month old SHR and WKY. Current-voltage relationships for I-Kl were completely superimposable in all groups. Conclusions: Prolongation of action potential in the hypertrophied heart of SHR is due to specific alterations in the repolarising potassium current I-to. The phenomenon is directly related to the duration of hypertension.