Effects of thyroid hormone on calcium handling in cultured chick ventricular cells.

Abstract

Mechanisms underlying thyroid hormone-induced changes in myocardial contractile state were investigated by studying the effects of triiodothyronine (T3) on Ca2+ fluxes across the sarcolemmal membrane and Ca2+ handling by the sarcoplasmic reticulum, using spontaneously contracting monolayers of cultured chick embryo ventricular cells. Cells were grown in serum-free medium containing either no T3 or 10(-8) M-T3 for 48 h. At [Ca2+]o levels of 0.6 and 1.2 mM, the velocity of cell contraction was significantly greater in cells grown in 10(-8) M-T3 than in its absence. At higher [Ca2+]o, no differences in the velocity of contraction were noted. 45Ca2+ exchange kinetic studies showed a biexponential pattern with a rapid and a slow component of uptake in cells grown both with and without 10(-8) M-T3. The rate of the rapid phase of uptake and total Ca2+ content were higher in cells grown in T3, with the increment in content ascribable to the rapidly exchangeable Ca2+ pool. Verapamil partially inhibited the T3-induced increase in the rapidly exchangeable pool. 45Ca2+ uptake in response to a step change to Na+-free medium in the presence of 1 microM-verapamil was significantly greater in cells grown in 10(-8) M-T3 than in T3-free medium. Cells grown in T3 showed 20% greater beating rate than cells grown in its absence. A similar increase in beating rate achieved by lowering [K+]o from 4.0 to 3.0 mM or by electrical stimulation failed to affect the rate of 45Ca2+ uptake or the size of the rapidly exchangeable pool; pacing-induced increases in rate resulted in reduction rather than augmentation of contractile state. Ca2+ efflux rate was greater in cells grown in 10(-8) M-T3 than in T3-free medium, whereas cells loaded with various levels of Ca2+ acutely by incubation at selected [Ca2+]o levels had similar efflux rates. Replacement of Na+ by choline in the efflux medium resulted in elevated Ca2+ efflux rates in cells grown both with and without T3; however, it remained greater in cells grown in 10(-8) M-T3 than in its absence. Caffeine (20 mM) in the efflux medium increased Ca2+ efflux to a greater degree in cells grown in T3 than without it. Caffeine also produced a greater tonic contraction in T3-treated cells than in cells grown in absence of T3 in Na+- and Ca2+-free medium.(ABSTRACT TRUNCATED AT 400 WORDS)