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L-type calcium current of isolated rat cardiac myocytes in experimental uraemia
P Donohoe1, A C McMahon, O V Walgama
1Department of Renal Medicine, GKT School of Medicine, King's College London, UK.
Insights
End-stage renal failure in rats accelerated L-type calcium channel inactivation in heart cells, shortening action potential duration. This finding suggests a mechanism for cardiac dysfunction in kidney disease.
Area of Science:
- Cardiology
- Nephrology
- Electrophysiology
Background:
- End-stage renal failure (ESRF) is linked to cardiac dysfunction, including cardiomyopathy and left ventricular hypertrophy.
- Cardiac issues are common in dialysis patients and predict mortality.
- L-type calcium channels are crucial for cardiac excitation-contraction coupling.
Purpose of the Study:
- To investigate the impact of subtotal nephrectomy (SNx) in rats on cardiac L-type calcium currents.
- To assess the effect of SNx on cardiac action potential duration in rats.
Main Methods:
- Wistar rats underwent two-stage SNx or sham surgery (bilateral renal decapsulation).
- Whole-cell patch clamp electrophysiology was used to measure L-type calcium currents in isolated ventricular myocytes.
- Epicardial monophasic action potentials were recorded from isolated perfused hearts.
Main Results:
- No significant difference in L-type calcium current amplitude or current-voltage relationships between SNx and control rats.
- Increased inactivation rate of L-type calcium current (15-25%) in myocytes from SNx rats.
- Shortened action potential duration (APD33) by approximately 20% in hearts from SNx rats.
Conclusions:
- Renal failure is associated with accelerated inactivation of cardiac L-type calcium currents.
- This rapid inactivation may decrease calcium influx.
- The findings suggest a potential mechanism contributing to shortened action potential duration in renal failure.
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. Ca(2+) influx through voltage-gated L-type Ca(2+) 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 Ca(2+) 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 Ca(2+) channel currents in isolated cardiac myocytes at 37 degrees 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 Ca(2+) current were not significantly different in myocytes from C (n=11) and SNx (n=8) rats. However, the rate of inactivation of the Ca(2+) current was increased by approximately 15-25% (P<0. 05) in myocytes from SNx rats. The action potential duration (APD(33)) at the apex of the left ventricle was approximately 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 Ca(2+) currents, which may reduce Ca(2+) influx and contribute to shortening of the action potential duration.