l-Triiodothyronine acutely increases Ca2+ uptake in the isolated, perfused rat heart. Changes in l-type Ca2+ channels and β-receptors during short- and long-term hyper- and hypothyroidism

Gøtzsche LB-H. l-Triiodothyronine acutely increases Ca2+ uptake in the isolated, perfused rat heart. Changes in l-type Ca2+ channels and β-receptors during short- and long-term hyper- and hypothyroidism. Eur J Endocrinol 1994;130:171–9. ISSN 0804–4643 Acutely administered triiodothyronine (T3) in supraphysiological doses has been shown to exert an acute positive inotropic effect in vivo a few minutes after intravenous administration. To investigate whether this effect could be explained by an acutely increased Ca2+ uptake in the myocardium, an isolated perfused rat heart model ad modum Langendorff was established. The acute stimulative effect of T3 on myocardial Ca2+ uptake was determined indirectly by measuring changes in Ca2+ concentration in the perfusate following coronary perfusion with 45Ca2+-containing buffer. Perfusion with T3 gave rise to dose-dependent reductions in perfusate Ca2+ within 20 s. Following 10−9 and 10−11 mol/l T3, the effect was small and usually lasted less than 1 min. Perfusion with 10−6 and 10−7 mmol/l T3 resulted in a decrease in perfusate Ca2+, which remained stable throughout 4–6 min of observation. Calcium channel blockade with nifedipine prevented the decrease in perfusate Ca2 +, suggesting that voltage-operated Ca2+ channels are involved in the increased Ca2 + uptake. A washout period with T3-free buffer re-established the Ca2+ concentration in the perfusate, suggesting that the effect is reversible. Calcium channels have been suggested to be regulated directly by T3. Maximum binding capacities for myocardial Ca2+ channels and β-receptors were determined by binding studies with [3H]PN200-110 and [125I]iodocyanopindolol in short-term and long-term hyper- and hypothyroid rats. After 2 and 8 weeks, Ca2+-channel maximum binding capacities were reduced by 25% and 23% in hyperthyroid rats (p<0.05) and increased by 33% and 23% in hypothyroid rats (p<0.05). β-Receptor binding capacities were increased by 33% and 50% in hyperthyroid rats (p<0.05) and reduced by 28% and 47% (p<0.05) in hypothyroid rats. The reduced Ca2+-channel maximum binding capacity during chronic hyperthyroidism is hypothesized to be a secondary event to a T3-induced increase in myocardial Ca2+ uptake in hyperthyroid rats, serving a protective role against Ca2+ overloading of the cell. The acute increase in Ca2+ uptake following T3 administration may explain the reported acute inotropic effect of T3. Liv Bjørn-Hansen Gøtzsche, Medical Department (Diabetes and Endocrinology), Århus Kommunehospital, University Hospital of Århus, DK-8000 Århus C, Denmark