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 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.
Donohoe
P
P
Department of Renal Medicine, GKT School of Medicine, King's College London, UK.
McMahon
A C
AC
Walgama
O V
OV
Bertaso
F
F
Dockrell
M E
ME
Cramp
H A
HA
Mullen
A M
AM
Shattock
M J
MJ
Hendry
B M
BM
James
A F
AF
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006352:Heart Ventricles; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials; D009392:Nephrectomy; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000503:physiopathology*
D020746:Calcium Channels, L-Type