1. Expression and phosphorylation of the [Na.sup.+]-[Cl.sup.-] cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1
- Author
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Vallon, Volker, Schroth, Jana, Lang, Florian, Kuhl, Dietmar, and Uchida, Shinichi
- Subjects
Gene expression -- Research ,Gene expression -- Physiological aspects ,Phosphorylation -- Research ,Phosphorylation -- Physiological aspects ,Salts -- Research ,Salts -- Physiological aspects ,Potassium in the body -- Research ,Potassium in the body -- Physiological aspects ,Biological sciences - Abstract
The Na-Cl cotransporter NCC is expressed in the distal convoluted tubule, activated by phosphorylation, and has been implicated in renal NaCl and [K.sup.+] homeostasis. The serum and glucocorticoid inducible kinase l (SGK1) contributes to renal NaCl retention and [K.sup.+] excretion, at least in part, by stimulating the epithelial [Na.sup.+] channel and [Na.sup.+]-[K.sup.+]-ATPase in the downstream segments of aldosterone-sensitive [Na.sup.+]/[K.sup.+] exchange. In this study we confirmed in wild-type mice (WT) that dietary NaCl restriction increases renal NCC expression and its phosphorylation at [Thr.sup.53], [Thr.sup.58], and [Ser.sup.71], respectively. This response, however, was attenuated in mice lacking SGK1 ([Sgk1.sup.-/-]), which may contribute to impaired NaCl retention in those mice. Total renal NCC expression and phosphorylation at [Thr.sup.53], [Thr.sup.58], and [Ser.sup.71] in WT were greater under low- compared with high-[K.sup.+] diet. This finding is consistent with a regulation of NCC to modulate [Na.sup.+] delivery to downstream segments of [Na.sup.+]/[K.sup.+] exchange, thereby modulating [K.sup.+] excretion. Dietary [K.sup.+]-dependent variation in renal expression of total NCC and phosphorylated NCC were not attenuated in [Sgk1.sup.-/-] mice. In fact, high-[K.sup.+] diet-induced NCC suppression was enhanced in [Sgk1.sup.-/-] mice. The hyperkalemia induced in [Sgk1.sup.-/-] mice by a high-[K.sup.+] diet may have augmented NCC suppression, thereby increasing [Na.sup.+] delivery and facilitating [K.sup.+] excretion in downstream segments of impaired [Na.sup.+]/[K.sup.+] exchange. In summary, changes in NaCl and [K.sup.+] intake altered NCC expression and phosphorylation, an observation consistent with a role of NCC in NaCl and [K.sup.+] homeostasis. The two maneuvers dissociated plasma aldosterone levels from NCC expression and phosphorylation, implicating additional regulators. Regulation of NCC expression and phosphorylation by dietary NaCl restriction appears to involve SGK1. with-no-lysine kinases; diuretic; epithelial sodium channel; intake; sodium chloride
- Published
- 2009