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

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)