Effect of thyroid hormone on slow calcium channel function in cultured chick ventricular cells.

Abstract

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-adren- ergic 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-PN200- 110 binding sites, (b) 24% (P < 0.05) more beta-adrenergic an- tagonist 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 con- centration ([Cali) measured with fura-2, total protein content, and, dissociation constant values for 3H-PN200-110 or H- CGP12177 binding was not significantly different in the two groups of cells. BAY k 8644 (1 MM) increased mean [Cab 2.85- or 2.16-fold in cells grown with or without 10 nM T3, respectively. l-Isoproterenol (1 ,uM) increased [Ca 1.53-or 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. by which thyroid hormone alters myocardial contractile state are not fully understood. Several studies have demonstrated the ability of thyroid hormone to increase myosin ATPase activity in the rat and rabbit by shifting the relative proportions of iso- enzyme forms such that the form with higher ATPase activity (Vl) predominates These findings have led to the hy- pothesis that enhancement of myocardial contractility by thyroid hormones is the result of increased cardiac myosin ATPase ac-