title: L-type calcium current of isolated rat cardiac myocytes in experimental uraemia.
abstract: 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.
authors.affiliation: Department of Renal Medicine, GKT School of Medicine, King's College London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Donohoe
authors.forename: A C
authors.initials: AC
authors.lastname: McMahon
authors.forename: O V
authors.initials: OV
authors.lastname: Walgama
authors.forename: F
authors.initials: F
authors.lastname: Bertaso
authors.forename: M E
authors.initials: ME
authors.lastname: Dockrell
authors.forename: H A
authors.initials: HA
authors.lastname: Cramp
authors.forename: A M
authors.initials: AM
authors.lastname: Mullen
authors.forename: M J
authors.initials: MJ
authors.lastname: Shattock
authors.forename: B M
authors.initials: BM
authors.lastname: Hendry
authors.forename: A F
authors.initials: AF
authors.lastname: James
mesh_terms: 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*
chemical_list: D020746:Calcium Channels, L-Type