Journal Article

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

Paul Donohoe, Aisling C. McMahon, Omal V. Walgama, Federica Bertaso, Mark E. C. Dockrell, Hilary A. Cramp, Adrian M. Mullen, Michael J. Shattock, Bruce M. Hendry and Andrew F. James

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 15, issue 6, pages 791-798
Published in print June 2000 | ISSN: 0931-0509
Published online June 2000 | e-ISSN: 1460-2385 | DOI:
L‐type calcium current of isolated rat cardiac myocytes in experimental uraemia

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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

Journal Article.  4067 words.  Illustrated.

Subjects: Nephrology

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