Effect of T 3 on Numbers of Slow Calcium Channels and Beta - Adrenergic Receptors in Cultured Heart Cells

The hyperthyroid state is associated with increased myocardial contractility. To clarify responsible mechanisms, we examined the effects of thyroid hormone on slow Ca channels, beta-adrenergic receptors, transsarcolemmal 45Ca flux and cytosolic free calcium in cultured chick ventricular cells. Compared with cells grown without triiodothyronine (T3), cells grown in 10 nM T3 possessed (a) 67% (P < 0.05) more dihydropyridine 3H-PN200110 binding sites, (b) 24% (P < 0.05) more beta-adrenergic antagonist 3H-CGP12177 binding sites, (c) a 57% (P < 0.05) greater nifedipine-sensitive initial 45Ca uptake rate, and (d) a 31% (P < 0.05) greater nifedipine-sensitive 45Ca uptake rate in response to BAY k 8644. Time-averaged mean intracellular free Ca concentration ([Cali) measured with fura-2, total protein content, and, dissociation constant values for 3H-PN200-110 or HCGP12177 binding was not significantly different in the two groups of cells. BAY k 8644 (1 MM) increased mean [Cab 2.85or 2.16-fold in cells grown with or without 10 nM T3, respectively. l-Isoproterenol (1 ,uM) increased [Ca 1.53or 1.28-fold in cells grown with or without 10 nM T3, respectively. We conclude that thyroid hormone augments transsarcolemmal Ca influx, at least in part via slow Ca channels associated with increased numbers of these channels. T3-treated cells appear to be more responsive to the effects of BAY k 8644 or isoproterenol on [Cali.