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Regulation of cardiac sarcolemmal Ca2+ channels and Ca2+ transporters by thyroid hormone

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Abstract

In order to examine the regulatory role of thyroid hormone on sarcolemmal Ca2+-channels, Na+−Ca2+ exchange and Ca2+-pump as well as heart function, the effects of hypothyroidism and hyperthyroidism on rat heart performance and sarcolemmal Ca2+-handling were studied. Hyperthyroid rats showed higher values for heart rate (HR), maximal rates of ventricular pressure development+(dP/dt)max and pressure fall−(dP/dt)max, but shorter time to peak ventricular pressure (TPVP) and contraction time (CT) when compared with euthyroid rats. The left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP), as well as aortic systolic and diastolic pressures (ASP and ADP, respectively) were not significantly altered. Hypothyroid rats exhibited decreased values of LVSP, HR, ASP, ADP, +(dP/dt)max and −(dP/dt)max but higher CT when compared with euthyroid rats; the values of LVEDP and TPVP were not changed. Studies with isolated-perfused hearts showed that while hypothyroidism did not modulate the inotropic response to extracellular Ca2+ and Ca2+ channel blocker verapamil, hyperthyroidism increased sensitivity to Ca2+ and decreased sensitivity to verapamil in comparison to euthyroid hearts. Studies of [3H]-nitrendipine binding with purified cardiac sarcolemmal membrane revealed decreased number of high affinity binding sites (Bmax) without any change in the dissociation constant for receptor-ligand complex (Kd) in the hyperthyroid group when compared with euthyroid sarcolemma; hypothyroidism had no effect on these parameters. The activities of sarcolemmal Ca2+-stimulated ATPase, ATP-dependent Ca2+ uptake and ouabain-sensitive Na+−K+ ATPase were decreased whereas the Mg2+-ATPase activity was increased in hypothyroid hearts. On the other hand, sarcolemmal membranes from hyperthyroid samples exhibited increased ouabain-sensitive Na+−K+ ATPase activity, whereas Ca2+-stimulated ATPase, ATP-dependent Ca2+ uptake, and Mg2+-ATPase activities were unchanged. The Vmax and Ka for Ca2+ of cardiac sarcolemmal Na+−Ca2+ exchange were not altered in both hyperthyroid and hypothyroid states. These results indicate that the status of sarcolemmal Ca2+-transport processes is regulated by thyroid hormones and the modification of Ca2+-fluxes across the sarcolemmal membrane may play a crucial role in the development of thyroid state-dependent contractile changes in the heart.

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Authors and Affiliations

  1. Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, R2H 2A6, Winnipeg, Manitoba, Canada

    Enn K. Seppet, Frantisek Kolar, Ian M. C. Dixon, Tomoji Hata & Naranjan S. Dhalla

  2. Department of Physiology, Faculty of Medicine, University of Manitoba, R2H 2A6, Winnipeg, Manitoba, Canada

    Enn K. Seppet, Frantisek Kolar, Ian M. C. Dixon, Tomoji Hata & Naranjan S. Dhalla

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Seppet, E.K., Kolar, F., Dixon, I.M.C. et al. Regulation of cardiac sarcolemmal Ca2+ channels and Ca2+ transporters by thyroid hormone. Mol Cell Biochem 129, 145–159 (1993). https://doi.org/10.1007/BF00926363

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