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Reduced sodium currents in isolated mammalian myocytes treated with chronic L ‐thyroxine
Author(s) -
Ma YuPing,
Hu HuiJuan,
Hao XueMei,
Zhou PeiAi,
Wu CaiHong,
Dai DeZai
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10138
Subject(s) - medicine , myocyte , endocrinology , chemistry , patch clamp , guinea pig , electrophysiology , biology
Whole‐cell patch‐clamp recording techniques were applied to measure I Na in isolated ventricular myocytes of guinea pigs and CA1 neurons of hippocampus of Sprague‐Dawley rats treated with L ‐thyroxine (0.5 mg/kg i.p. for 8–10 days). We found that the I Na densities in both hypertrophied ventricular myocytes of guinea pigs and CA1 neurons of rats were reduced significantly. The peak current of −53.2±10.8 pA/pF (n=39) which was evoked at –30mV in the hypertrophied ventricular myocytes was significantly reduced when compared with –73.8±14.7 pA/pF in control myocytes (n=45, P <0.001). The maximal I Na densities (at –60 mV membrane potential) of CA1 neurons in L ‐thyroxine‐treated rats were reduced from 46.0±8.5 pA/pF to 38.9±8.3 pA/pF, respectively (n=20, P <0.05). After treatment with L ‐thyroxine, the decay of I Na both in the ventricular myocytes of guinea pigs and CA1 neurons of rats was faster. The τ was 3.7±0.1 and 4.1±0.2 ms in the hypertrophied and control myocytes ( P <0.05), respectively. The slow τ was accelerated from 3.87±1.28 in the control to 2.94±0.64 ms in the CA1 neurons of rats treated with L ‐thyroxine ( P <0.05). No differences were found in the steady‐state activation and inactivation and recovery kinetics in the hypertrophied ventricular myocytes. Our results indicate that impaired I Na is involved in the heart and neurons in hyperthyroidism. A compromised I Na for depolarization of the affected myocardium produces a slow conduction of cardiac impulses and provides a basis for uneven electrophysiological parameters. A reduced depolarizing I Na combined with an impaired ion current for repolarization contribute to arrhythmogenesis of the remodeled ventricle. Drug Dev. Res. 58:111–115, 2003. © 2003 Wiley‐Liss, Inc.