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 (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.
Scamps
F
F
Laboratoire de Physiologie Cellulaire Cardiaque, INSERM U-241, Université Paris-Sud, Orsay, France.
Mayoux
E
E
Charlemagne
D
D
Vassort
G
G
D000200:Action Potentials; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D006332:Cardiomegaly / Q000503:physiopathology*; D004056:Differential Threshold; D004553:Electric Conductivity; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006706:Homeostasis; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol; D002118:Calcium