title: An altered repolarizing potassium current in rat cardiac myocytes after subtotal nephrectomy.
abstract: Renal failure in humans is associated with electrocardiographic changes including altered QT interval dispersion, which suggests that cardiac myocyte repolarization is abnormal and which appears to correlate with cardiac prognosis. In this study, cardiac myocyte repolarizing currents have been studied in isolated cells from rats 8 wk after subtotal nephrectomy (SNx), using sham-operated animals as controls. In addition, monophasic cardiac action potentials were recorded from the epicardial surface of the left ventricle (LV) apex, LV base, and the right ventricle of isolated perfused hearts paced at 320/min. SNx was associated with cardiac hypertrophy and histologic evidence of myocardial fibrosis, but SNx rats were not hypertensive. Repolarizing K(+) currents were measured using whole-cell patch-clamp, and 4-aminopyridine (4-AP)-sensitive transient outward (I(to)) and 4-AP-insensitive sustained outward (I(so)) components were quantified. After SNx, I(to) was increased by two to threefold at voltages from -30 to +60 mV and showed increased heterogeneity. For example, at 0 mV voltage clamp pulse, the median I(to) was increased from 3.23 pA/pF in control myocytes (interquartile range 3.20 pA/pF, n = 24) to 5.86 pA/pF in SNx myocytes (interquartile range 7.32 pA/pF, n = 21, P: < 0.005). The kinetics of inactivation of I(to) were altered after SNx with slowing both of the onset and the recovery from inactivation. The mean time constant of inactivation at +30 mV after SNx was 14.2 +/- 1.6 ms (n = 20) compared with control values of 9.8 +/- 0.6 ms (n = 23, P: < 0.05). Neither I(so) nor inward rectifier K(+) currents were altered after SNx. The action potential duration (APD(50)) at the left ventricular base was approximately 20% shorter (P: < 0.02) in hearts from SNx rats compared with controls. 4-AP (2 mM) prolonged the APD(50) in all regions in hearts from both SNx and control rats and abolished the APD(50) shortening in SNx. These results indicate that abnormalities of the cardiac transient outward K(+) current contribute to alterations in the cardiac action potential in renal failure and warrant further investigation because they may contribute to altered repolarization and arrythmogenesis.
authors.affiliation: Department of Renal Medicine, Guy's King's and St. Thomas' School of Medicine, King's College London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Donohoe
authors.affiliation: Department of Renal Medicine, Guy's King's and St. Thomas' School of Medicine, King's College London, United Kingdom.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Hendry
authors.affiliation: Rayne Institute, St. Thomas' Hospital, Guy's King's and St. Thomas' School of Biomedical Sciences, King's College London, United Kingdom.
authors.forename: Omal V
authors.initials: OV
authors.lastname: Walgama
authors.affiliation: Department of Renal Medicine, Guy's King's and St. Thomas' School of Medicine, King's College London, United Kingdom.
authors.forename: Federica
authors.initials: F
authors.lastname: Bertaso
authors.affiliation: Department of Pathology, Guy's King's and St. Thomas' School of Medicine, King's College London, United Kingdom.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Hopster
authors.affiliation: Rayne Institute, St. Thomas' Hospital, Guy's King's and St. Thomas' School of Biomedical Sciences, King's College London, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shattock
authors.affiliation: Department of Renal Medicine, Guy's King's and St. Thomas' School of Medicine, King's College London, United Kingdom.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: James
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009392:Nephrectomy / Q000379:methods*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D012016:Reference Values; D016277:Ventricular Function, Left
chemical_list: D015221:Potassium Channels