Thyroid status and beta-agonistic effects on cytosolic calcium concentrations in single rat cardiac myocytes activated by electrical stimulation or high-K+ depolarization.

The effects of the thyroid status on the cytosolic free Ca2+ concentration (Ca2+]i) in single cardiomyocytes were studied at rest and during contraction. The mean resting Ca2+]i increased significantly from the hypothyroid (45 +/- 4 nM) through the euthyroid (69 +/- 12 nM) to the hyperthyroid condition (80 +/- 11 nM) at extracellular Ca2+ concentrations (Ca2+]o) up to 2.5 mM. At Ca2+]o above 2.5 mM the differences in Ca2+]i between the groups became less. The amplitude of the Ca2+ transients became higher in all groups with increasing Ca2+]o (1, 2.5 and 5 mM), and was highest at all Ca2+]o in hyperthyroid myocytes. The beta-agonist isoprenaline elevated peak Ca2+]i during contraction and increased the rate of the decay of the Ca2+ transients to a greater extent in hypothyroid myocytes than in hyperthyroid myocytes. Depolarization with high K+]o induced a large but transient Ca2+]i overshoot in hypothyroid myocytes, but not in hyperthyroid myocytes, before a new elevated steady-state Ca2+]i was reached, which was not different between the groups. When isoprenaline was added to K+ o-depolarized myocytes after a steady state was reached, a significantly larger extra increase in Ca2+]i was measured in the hypothyroid group (28%) compared with the hyperthyroid group (8%). It is concluded that in cardiac tissue exposed to increasing amounts of thyroid hormones (1) Ca2+]i increases at rest and during contraction in cardiomyocytes and (2) interventions which favour Ca2+ entry into the cytosol ( Ca2+]o elevation, high K+]o, beta-agonists) tend to have less impact on Ca2+ homoeostasis.