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

Background. End-stage renal failure is associated with a low-output cardiomyopathy, left ventricular hyper- rectomy model; uraemic cardiomyopathy; whole-cell patch-clamp trophy 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 Introduction key role in the excitation–contraction coupling of cardiac myocytes. The purpose of this study was to End-stage renal failure is associated with a 10-fold examine the effect of subtotal nephrectomy (SNx) in increase in age-matched cardiovascular mortality [1] the rat on both cardiac L-type Ca2+ currents and and a cardiomyopathy associated with low output left action potential duration. ventricular failure [2], left ventricular hypertrophy [3], Methods. Wistar rats underwent two-stage SNx; con- myocardial fibrosis [4] as well as increased intra-ECG trol rats (C ) underwent bilateral renal decapsulation. variation in QT interval (‘QT dispersion’), which has Animals were sacrificed after 8 weeks, and ventricular been associated with an increased risk of sudden death myocytes were isolated. SNx rats showed a 2-fold [5]. The aetiology of this cardiomyopathy is complex, increase in plasma urea and creatinine compared with but is likely to include hypertension, anaemia, secondC rats. Whole-cell patch clamp techniques were used ary hyperparathyroidism, acidosis and uraemic toxins. to examine L-type Ca2+ channel currents in isolated The cardiomyopathy is prevalent in patients just begincardiac myocytes at 37°C. In separate experiments, the ning regular dialysis therapy and is an important epicardial monophasic action potentials of isolated indicator of subsequent mortality [6 ]. perfused whole hearts from C and SNx rats were It is clear from animal work that renal failure is