Nephrol Dial Transplant (2000) 15: 791-798
© 2000 European Renal Association-European Dialysis and Transplant Association
L-type calcium current of isolated rat cardiac myocytes in experimental uraemia
Department of Renal Medicine, GKT School of Medicine, King's College London, 1 Anthony Raine Research Laboratories, St. Bartholomew's Hospital, Queen Mary Westfield College, 2 Cardiac Surgical Research and 3 Cardiovascular Research, The Rayne Institute, Centre for Cardiovascular Biology and Medicine, St. Thomas' Hospital, King's College London, London, UK
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.
Keywords: cardiac action potential duration; isolated cardiac myocytes; L-type Ca2+ currents; partial nephrectomy model; uraemic cardiomyopathy; whole-cell patch-clamp
Correspondence and offprint requests to: Dr A. F. James, Department of Renal Medicine, GKT School of Medicine, King's College London, Bessemer Road, London SE5 9PJ, UK.
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