L-type calcium current of isolated rat cardiac myocytes in experimental uraemia

Abstract

Background. End-stage renal failure is associated with a low-output cardiomyopathy, left ventricular hypertrophy and increased QTc dispersion. Cardiac dysfunction is prevalent in patients at the beginning of dialysis and is an important predictor of mortality. Ca2+ influx through voltage-gated L-type Ca2+ channels plays a key role in the excitation-contraction coupling of cardiac myocytes. The purpose of this study was to examine the effect of subtotal nephrectomy (SNx) in the rat on both cardiac L-type Ca2+ currents and action potential duration. Methods. Wistar rats underwent two-stage SNx; control rats (C) underwent bilateral renal decapsulation. Animals were sacrificed after 8 weeks, and ventricular myocytes were isolated. SNx rats showed a 2-fold increase in plasma urea and creatinine compared with C rats. Whole-cell patch clamp techniques were used to examine L-type Ca2+ channel currents in isolated cardiac myocytes at 37°C. In separate experiments, the epicardial monophasic action potentials of isolated perfused whole hearts from C and SNx rats were recorded. Results. The amplitude and current-voltage relationships of the L-type Ca2+ current were not significantly different in myocytes from C (n = 11) and SNx (n = 8) rats. However, the rate of inactivation of the Ca2+ current was increased by ~ 15-25% (P < 0.05) in myocytes from SNx rats. The action potential duration (APD33) at the apex of the left ventricle was ~ 20% shorter (P < 0.01) in hearts from SNx rats as compared with controls. Conclusions. Renal failure is associated with rapid inactivation of cardiac ventricular myocyte L-type Ca2+ currents, which may reduce Ca2+ influx and contribute to shortening of the action potential duration.