Reduction of the transient outward potassium current in canine x‐linked muscular dystrophy
作者:
Linda Pacioretty,
Barry Cooper,
Robert Gilmour,
期刊:
Circulation
(OVID Available online 1994)
卷期:
Volume 90,
issue 3
页码: 1350-1356
ISSN:0009-7322
年代: 1994
出版商: OVID
关键词: electrophysiology;ions;cardiovascular diseases;cardiomyopathy
数据来源: OVID
摘要:
BackgroundThexmddog develops a cardiomyopathy similar to that seen in Duchenne muscular dystrophy patients. In both the canine and human diseases, ECG abnormalities may precede the development of overt cardiac pathological lesions. The purpose of this study was to determine whether specific cellular electrical abnormalities occur in dystrophic ventricular tissue.Methods and ResultsAction potentials were recorded in epicardial tissue strips obtained from normal and xmd dogs. Phase 1 amplitude was increased from 86.8±2.7 mV in normal dogs to 94.3± 1.8 mV inxmddogs (mean±SEM;P<.05). The 4-aminopyridine-sensitive transient outward potassium current (Ito), as recorded in isolated epicardial myocytes using the whole-cell patch-clamp technique, was reduced in xmd dogs compared with age-matched normal dogs. Cell capacitance also was reduced significantly inxmdcompared with normal cells, as was the current density (3.6±0.3 versus 5.4±0.8 pA/pF, respectively). No differences were observed in the time constants of current decay or in the kinetics of recovery from inactivation between groups. The slope factor (k) of steadystate inactivation was significantly greater inxmdcompared with normal cells (7.2±0.9 versus 5.4±0.5, respectively), whereas the V1/2of inactivation did not differ (−38.2±2.4 versus −36.8±1.6 mV, respectively).ConclusionsThese data indicate that the magnitude of Ito, is reduced in dystrophic epicardial myocytes, resulting in an increase in phase 1 amplitude. The reduction of Itomay alter the balance of inward and outward currents in dystrophic myocardium and thereby contribute to the development of cardiac pathology.
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