Calcium current in single cells isolated from normal and hypertrophied rat heart. Effects of beta-adrenergic stimulation.

ABSTRACT

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 (ICa) by a beta-adrenergic agonist (isoproterenol) was also analyzed since beta-agonist-induced positive inotropy is less marked in hypertrophied heart. Left ventricular hypertrophy was induced by stenosis of the abdominal aorta. For recording ICa, 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 microM 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 ICa 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, ICa displayed the same voltage and time dependence. When expressed as a percentage, the maximal increase in ICa amplitude that was obtained with 100 nM isoproterenol was less in hypertrophied cells (+78%) than in normal cells (+120%). The sensitivity of ICa to beta-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 ICa by beta-adrenergic agonist was decreased in agreement with a reduced number of binding sites of beta-agonists and/or an altered coupling of the G-proteins.