CALCIUM CURRENT IN SINGLE CELLS ISOLATED FROM NORMAL AND HYPERTROPHIED RAT-HEART - EFFECTS OF BETA-ADRENERGIC STIMULATION

The L-type calcium current was investigated in normal and hypertrophied rat ventricular myocytes as a possible cause of the action potential lengthening that has been reported during hypertrophy. Regulation of the calcium current (I(Ca)) by a β-adrenergic agonist (isoproterenol) was also analyzed since β-agonist-induced positive inotropy is less marked in hypertrophied heart. Left ventricular hypertrophy was induced by stenosis of the abdominal aorta. For recording I(Ca), the whole-cell patch-clamp technique was used. Potassium currents were suppressed by replacing K+ ions with Cs+ ions in both the extracellular and intracellular media, and sodium current was blocked by 50 μM tetrodotoxin. The Ca2+ current was larger in hypertrophied cells (2.2 ± 0.6 nA [n = 31]) than in normal cells (1.2 ± 0.5 nA [n = 33]). However, if one relates I(Ca) amplitude to the cell membrane area, as estimated by membrane capacitance measurement, no significant difference was observed in current density (8.5 ± 2.5 pA/pF [n = 31] and 8.3 ± 2.1 pA/pF [n = 33] in hypertrophied and in normal cells, respectively). In both cell types, I(Ca) displayed the same voltage and time dependence. When expressed as a percentage, the maximal increase in I(Ca) amplitude that was obtained with 100 nM isoproterenol was less in hypertrophied cells (+78%) than in normal cells (+120%). The sensitivity of I(Ca) to β-adrenergic stimulation was not modified: EC50 was 3.8 nM for hypertrophied cells and 4.8 nM for normal cells. Forskolin and cyclic AMP were as effective in both cell types. Stimulation of I(Ca) by β-adrenergic agonist was decreased in agreement with a reduced number of binding sites of β-agonists and/or an altered coupling of the G-proteins.