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

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 IN, 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 IN., 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 tau was 3.7+/-0.1 and 4.1+/-0.2 ms in the hypertrophied and control myocytes (P<0.05), respectively. The slow tau 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. (C) 2003 Wiley-Liss, Inc.