L-type calcium current in catecholamine-induced cardiac hypertrophy in the rat.
This study investigates whether an increase in L-type calcium current (ICa) could explain the prolongation of the action potential associated with the cardiac hypertrophy produced by repeated administration of isoprenaline. Hypertrophy was induced by daily injection of isoprenaline (5 mg/kg i.p.) for 7 days in male Wistar rats. Under whole-cell voltage-clamp conditions, ICa was evoked in Na(+)- and K(+)-free solution, by step depolarizations from a holding potential of -45 mV in single left ventricular myocytes isolated from control and hypertrophied rat hearts. In the test group, heart weight to body weight ratio and cell membrane capacitance were increased by 30 and 34%, respectively. Peak ICa was increased by 26% (control, -1.46 +/- 0.06 nA, n = 17; hypertrophy, -1.85 +/- 0.13 nA, n = 19; P < 0.02). However, when normalized for cell capacitance, there was no significant difference in peak current density (control, -12.1 +/- 0.5 pA/pF; hypertrophy, -11.5 +/- 0.6 pA/pF). The voltage dependence of ICa was similar in both cell types. No change was observed either in the steady-state activation or inactivation kinetics, or in the time course of inactivation. The recovery from inactivation of ICa, when fitted with monoexponential function with time constant tau rec, was not changed significantly by hypertrophy (control, tau rec = 115 +/- 23 ms, n = 9; hypertrophy, tau rec = 120 +/- 12 ms, n = 15). The increased calcium current occurs in parallel with the increase in cell size. The prolonged action potential duration seen in this model must be explained by changes in currents other than L-type calcium current.
Mészáros
J
J
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, UK.
Coutinho
J J
JJ
Bryant
S M
SM
Ryder
K O
KO
Hart
G
G
D000200:Action Potentials / Q000502:physiology; D000318:Adrenergic beta-Agonists; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D002395:Catecholamines / Q000502:physiology; D004594:Electrophysiology; D066298:In Vitro Techniques; D007545:Isoproterenol; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D002395:Catecholamines; D007545:Isoproterenol