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 difference 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 β-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), β-agonists) tend to have less impact on Ca2+ homoeostasis.