ACUTE THYROID-HORMONE PROMOTES SLOW INACTIVATION OF SODIUM CURRENT IN NEONATAL CARDIAC MYOCYTES

Sodium current (I(Na)) inactivation kinetics in neonatal cardiac myocytes were analyzed using whole cell voltage clamp before and after acute treatments with thyroid hormone (3,5,3'-triiodo-L-thyronine, T3). In untreated neonatal myocytes, I(Na) inactivation was predominantly mono-exponential, with 93 +/- 3% (S.D.; n = 9) of the peak amplitude decaying with a time constant, tau-h1, of 1.8 +/- 0.5 ms at -30 mV. The remaining 7% of control I(Na) decayed more slowly, with a time constant, tau-h2, of 9.3 +/- 3.0 ms at -30 mV. The contribution of slowly-inactivating channels to peak current was increased from 7% to 43 +/- 27% within 5 min of exposure to 5-20 nM T3 (nine cells; P < 0.005). The time constants for both the fast- and slow-inactivating components of peak current (tau-h1 and tau-h2) were not significantly changed by acute T3 treatment, nor was steady-state I(Na) inactivation (h infinity) affected. Thyroid hormone action on sodium inactivation was partially reversible by lidocaine. These findings indicate that T3 acts at the neonatal cardiac cell membrane to promote slow inactivation kinetics in sodium channels.