REGULATION OF NA+/K+ TRANSPORT BY THYROID HORMONE

本申请中提出的研究旨在获得更多 对细胞阳离子转运调控的全面认识 甲状腺激素。特别是申请人已经提出，并开始 测试，假设已知的活性钠刺激和 钾通过甲状腺激素的运输，而不是归因于 Na，K泵(Na，K-ATPase)的初级诱导 相反，推测是更近端的荷尔蒙增强的结果 钠和/或钾在细胞膜上的被动泄漏。 申请人的初步研究通过以下方式支持了这一假设 不仅证明了体内甲状腺激素治疗确实 增加大鼠离体膜和膜的被动钾外流 肝脏切片，但这种效应早在6月份就出现了 在注射T3后数小时，并基本上在任何诱导 Na，K-ATPase本身。体内效应的进一步研究 甲状腺激素对大鼠肝切片阳离子转运的影响 建议更好地描述这种被动的荷尔蒙刺激 钾外流。在培养细胞(主要是大鼠)中的其他研究 肝细胞)将检测甲状腺激素在体外对 被动通量和胞内钠离子浓度 钾，被动阳离子通量在调节刺激中的作用 甲状腺激素对活性阳离子转运的影响及其与 T_3诱导的被动和主动阳离子通量对 Na，K泵。希望这些详细的调查将 此外，还有助于更好地理解变化可能起的作用 在调节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.