Reduced sodium currents in isolated mammalian myocytes treated with chronic L‐thyroxine

Abstract

AbstractWhole‐cell patch‐clamp recording techniques were applied to measure INa 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 INa 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 INa 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 INa 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 INa is involved in the heart and neurons in hyperthyroidism. A compromised INa for depolarization of the affected myocardium produces a slow conduction of cardiac impulses and provides a basis for uneven electrophysiological parameters. A reduced depolarizing INa 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.