Effect of thyroid state on cytosolic free calcium in resting and electrically stimulated cardiac myocytes

Abstract The effects of the thyroid state on the cytosolic free Ca 2+ concentration, [Ca 2+ ] i , of resting and K + -depolarized cardiomyocytes were studied using the fluorescent Ca 2+ indicator fura2. The mean resting [Ca 2+ ] i in euthyroid myocytes ( 89 ± 8 nM ) was not significantly different from that in hyperthyroid myocytes ( 100 ± 14 nM ). The resting O 2 -consumption rate was identical for both groups when expressed per mg protein, but a 35% higher value was observed in the hyperthyroid group when expressed per cell on account of the cellular hypertrophy induced by thyroid hormone. Potassium induced depolarization (50 mM [K + ] 0 ) raised the level of [Ca 2+ ] i by 50% in both groups. When ATP-coupled respiration was blocked with oligomycin, the 50 mM K + -induced rise in [Ca 2+ ] i was accompanied in both groups by a 40% rise in glycolytic activity as inferred from measurement of lactate production. Ca 2+ -fluorescence transients were recorded from electrically stimulated myocytes of euthyroid, hyperthyroid and hypothyroid rats. The time taken to reach peak fluorescence (TPL) and that to 50% decay of peak fluorescence (RL 0.5 ) decreased in the direction hypothyroid → hyperthyroid, indicating an increase in Ca 2+ fluxes in the same direction. Isoproterenol (1 μM) enhanced the peak Ca 2+ fluorescence in electrically stimulated hypothyroid and euthyroid myocytes but not in hyperthyroid myocytes. Both the TPL and RL 0.5 were decreased by isoproterenol in euthyroid, but more so in hypothyroid myocytes. None of these parameters were influenced by isoproterenol in the hyperthyroid group. We conclude that (1) thyroid hormone increases neither the O 2 -consumption rate nor the level of [Ca 2+ ] i of resting cardiomyocytes and (2) the effects of the β-receptor-agonist isoproterenol on Ca 2+ transients of electrically stimulated myocytes, are inversely related to the documented changes in β-receptor density in heart tissue occurring with alterations in the thyroid state.