Acute thyroid hormone promotes slow inactivation of sodium current in neonatal cardiac myocytes.
Sodium current (INa) 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, INa 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 INa 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 less than 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 INa 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.
Harris
D R
DR
Research Service, Department of Veterans Affairs Medical Center, Brooklyn, NY 11209.
Green
W L
WL
Craelius
W
W
D000818:Animals; D000831:Animals, Newborn; D004553:Electric Conductivity / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology*
D015222:Sodium Channels; D014284:Triiodothyronine; D008012:Lidocaine; D012964:Sodium