REGULATION OF NA+/K+ TRANSPORT BY THYROID HORMONE

本申请中提出的研究旨在获得更好的性能。 完全理解细胞阳离子转运的调节， 甲状腺激素 特别是，申请人已经提出并开始 测试，假设已知的刺激活性钠和 钾通过甲状腺激素转运，而不是归因于 Na，K泵（Na，K-ATP酶）的初级诱导，如先前所述， 相反，假设是更近端的激素增强的结果 钠和/或钾穿过细胞膜的被动泄漏。 申请人的初步研究支持了这一假设， 这不仅证明了体内甲状腺激素治疗确实 增加从离体大鼠膈肌和 肝脏切片，但此外，这种影响是存在早在6 在注射T3后数小时，并且基本上在任何诱导T3之前， Na，K-ATPase本身。 进一步研究体内 甲状腺激素处理对大鼠肝片阳离子转运的影响 建议更好地描述这种被动的激素刺激， 钾外流 在培养细胞（主要是大鼠）中的其他研究 肝细胞）将检查甲状腺激素对 被动通量和细胞内钠浓度， 钾，被动阳离子通量在介导刺激中的作用 甲状腺激素主动阳离子转运，以及 T3引起的被动和主动阳离子通量的变化， 钠钾泵。 希望这些详细的调查将 此外，还可以更好地了解变化可能发挥的作用 在介导甲状腺激素作用的阳离子通量中。

The studies proposed in this application are aimed at obtaining a more complete understanding of the regulation of cellular cation transport by thyroid hormone. In particular the applicant has proposed, and begun to test, the hypothesis that the known stimulation of active sodium and potassium transport by thyroid hormone, rather than being attributable to a primary induction of the Na, K pump (Na,K-ATPase) as has previously been postulated, instead is the result of a more proximal hormonal enhancement of the passive leak of sodium and/or potassium across the cell membrane. Initial studies by the applicant have lent support to this hypothesis by demonstrating not only that in vivo thyroid hormone treatment does indeed increase passive potassium efflux from both isolated rat diaphragm and liver slices, but furthermore that this effect is present as early as 6 hours after an injection of T3, and substantially precedes any induction of the Na,K-ATPase itself. Further investigations of the effects of in vivo thyroid hormone treatment on cation transport in rat liver slices are proposed to better characterize this hormonal stimulation of passive potassium efflux. Additional studies in cultured cells (primarily rat hepatocytes) will examine the direct in vitro effect of thyroid hormone on both the passive fluxes and intracellular concentrations of sodium and potassium, the role of passive cation fluxes in mediating the stimulation of active cation transport by thyroid hormone, and the relationship of T3-induced changes in passive and active cation fluxes to the number of Na,K pumps. It is hoped that these detailed investigations will additionally lead to a better understanding of the possible role of changes in cation fluxes in mediating thyroid hormone action.