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

Background. End-stage renal failure is associated with a low-output cardiom yopathy, left ventricular hypertrophy and increased QTc dispersion. Cardiac dysfunction is prevalent in patients at the beginning of dialysis and is a n important predictor of mortality. Ca2+ influx through voltage-gated L-typ e 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 su btotal nephrectomy (SNx) in the rat on both cardiac L-type Ca2+ currents an d action potential duration. Methods. Wister rats underwent two-stage SNx; control rats (C) underwent bi lateral renal decapsulation. Animals were sacrificed after 8 weeks, and ven tricular myocytes were isolated. SNx rats showed a 2-fold increase in plasm a urea and creatinine compared with C rats. Whole-cell patch clamp techniqu es were used to examine L-type Ca2+ channel currents in isolated cardiac my ocytes at 37 degrees C. In separate experiments, the epicardial monophasic action potentials of isolated perfused whole hearts from C and SNx rats wer e 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 S Nx (n = 8) rats. However, the rate of inactivation of the Ca2+ current was increased by similar to 15-25% (P < 0.05) in myocytes from SNx rats. The ac tion potential duration (APD(33)) at the apex of the left ventricle was sim ilar to 20% shorter (P < 0.01) in hearts from SNx rats as compared with con trols. 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.