Role of Sgk1 in salt and potassium homeostasis

Abstract

Aldosterone plays a pivotal role in NaCl and K+homeostasis by stimulation of Na+reabsorption and K+secretion in the aldosterone-sensitive distal nephron (ASDN). Recent studies demonstrated that the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by aldosterone in the ASDN and that polymorphisms of the kinase associate with arterial blood pressure in normotensive subjects. This review discusses the role of Sgk1 in NaCl and K+homeostasis as evidenced by in vivo studies, including those in Sgk1-deficient mice. The studies indicate that Sgk1 is not absolutely required for Na+reabsorption and K+secretion in the ASDN. On a standard NaCl and K+diet, modestly enhanced plasma aldosterone concentrations appear sufficient to establish a compensated phenotype in the absence of Sgk1. The kinase is necessary, however, for upregulation of transcellular Na+reabsorption in the ASDN. This may involve Sgk1-mediated stimulation of basolateral Na+-K+-ATPase as well as retention of epithelial Na+channel, ENaC, in the apical membrane. Such an upregulation is a prerequisite for adequate adaptation of 1) renal NaCl reabsorption during restricted dietary NaCl intake, as well as 2) K+secretion in response to enhanced K+intake. Thus gain-of-function mutations of Sgk1 are expected to result in renal NaCl retention and enhanced K+secretion. Further studies are required to elucidate renal and nonrenal aldosterone-induced effects of Sgk1, the role of other Sgk1 activators, as well as the link of Sgk1 polymorphisms to arterial hypertension in humans.