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 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.