ACTION-POTENTIAL AND PLATEAU IONIC CURRENTS IN MODERATELY AND SEVERELY DOCA-SALT HYPERTROPHIED RAT HEARTS

Ventricular hypertrophy is associated with an increase in action poten tial (AP) plateau amplitude and duration. In a model of cardiac hypert rophy by DOCA-pellet implantation in uninephrectomized saline-drinking rats, we have previously demonstrated that the influence of hypertrop hy was to reduce I-to1 density, the process being fully reversible aft er elimination of DOCA pellets, In that study the decrease of I-to1 de nsity appeared to vary from moderate reduction to complete suppression which could explain, at least in part, the AP lengthening. In the pre sent study the effect of the degree of hypertrophy (moderate and sever e hypertrophy) was investigated on rat ventricular action potential pl ateau amplitude and duration, high threshold calcium current, I-Ca-L, Na-Ca exchange current, I-Na-Ca, transient outward potassium current, I-to1, and sustained outward potassium current, I-sus. Ventricular act ion potentials of isolated perfused hearts were recorded by means of s tandard floating microelectrodes and ionic currents of single ventricu lar myocytes were measured using the whole-cell recording patch-clamp technique. We show that: (1) AP plateau amplitude and duration increas e more markedly in severe than in moderate hypertrophy; (2) the decrea se in I-to1 density is much larger in severe than in moderate hypertro phy whereas I-Ca-L, I-Na-Ca and i(sus) densities remain unaltered in e ither state of hypertrophy. After suppression of I-to1 by 3 mM 4-amino pyridine, action potential plateau amplitude and duration remain incre ased in severely hypertrophied rat hearts compared to sham rats. There fore, although these results designate I-to1 reduction as the main cau se of hypertrophy-induced AP changes, those occurring in severe hypert rophy cannot be uniquely explained by a quasi-complete extinction of I -to1. (C) 1996 Academic Press Limited