Regulation of cardiac sarcolemmal Ca channels and Ca transporters by thyroid hormone.

Autor: Seppet, Enn, Kolar, Frantisek, Dixon, Ian, Hata, Tomoji, Dhalla, Naranjan
Zdroj: Molecular & Cellular Biochemistry; Dec1993, Vol. 129 Issue 2, p145-159, 15p
Abstrakt: In order to examine the regulatory role of thyroid hormone on sarcolemmal Ca-channels, Na−Ca exchange and Ca-pump as well as heart function, the effects of hypothyroidism and hyperthyroidism on rat heart performance and sarcolemmal Ca-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 Ca and Ca channel blocker verapamil, hyperthyroidism increased sensitivity to Ca and decreased sensitivity to verapamil in comparison to euthyroid hearts. Studies of [H]-nitrendipine binding with purified cardiac sarcolemmal membrane revealed decreased number of high affinity binding sites (B) without any change in the dissociation constant for receptor-ligand complex (K) in the hyperthyroid group when compared with euthyroid sarcolemma; hypothyroidism had no effect on these parameters. The activities of sarcolemmal Ca-stimulated ATPase, ATP-dependent Ca uptake and ouabain-sensitive Na−K ATPase were decreased whereas the Mg-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 Ca-stimulated ATPase, ATP-dependent Ca uptake, and Mg-ATPase activities were unchanged. The V and K for Ca of cardiac sarcolemmal Na−Ca exchange were not altered in both hyperthyroid and hypothyroid states. These results indicate that the status of sarcolemmal Ca-transport processes is regulated by thyroid hormones and the modification of Ca-fluxes across the sarcolemmal membrane may play a crucial role in the development of thyroid state-dependent contractile changes in the heart. [ABSTRACT FROM AUTHOR]
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