SGK1 is not required for regulation of colonic ENaC activity

The serum and glucocorticoid-inducible kinase SGK1 is known to be upregulated by mineralocorticoids and to enhance ENaC activity in several expression systems. Moreover, the amiloride-sensitive transepithelial potential difference in the collecting duct is lower in gene-targeted mice lacking SGK1 (sgk1 −/−) than in their wild-type littermates (sgk1 +/+). Accordingly, the ability of sgk1 −/− mice to decrease urinary sodium output during salt depletion is impaired. These observations highlight the importance of SGK1 in the stimulation of renal ENaC activity. In colonic epithelium, ENaC activity and, thus, transepithelial potential difference (V te) are similarly upregulated by mineralocorticoids. The present study thus explored V te and the apparent amiloride-sensitive equivalent short circuit current (I amil) in the colon from sgk1 −/− and sgk1 +/+ mice before and after treatment with low salt diet, the glucocorticoid dexamethasone [DEXA, 10 μg/g body weight (BW)], or the mineralocorticoid deoxycorticosterone acetate (DOCA, 1.5 mg/day). Surprisingly, V te and I amil were both significantly (p<0.05) higher in sgk1 −/− than in sgk1 +/+ untreated mice. A 7-day exposure to low salt diet increased V te and I amil in both genotypes, but did not abrogate the differences of V te and I amil between sgk1 −/− and sgk1 +/+ mice. Plasma aldosterone levels were significantly higher in sgk1 −/− than in sgk1 +/+ mice both under control conditions and under low salt diet, which may explain the enhanced V te in sgk1 −/− mice. Treatment with DEXA or DOCA both significantly increased V te and I amil in sgk1 +/+ mice and tended to increase V te and I amil in sgk1 −/− mice. Under treatment with DEXA or DOCA, V te and I amil were similar in sgk1 −/− and sgk1 +/+ mice. Fecal Na+ excretion was similar in sgk1 +/+ mice and in sgk1 −/− mice and was similarly decreased by low Na+ diet in both genotypes. In conclusion, transepithelial potential and amiloride-sensitive short circuit current are enhanced in the colonic epithelium of SGK1-deficient mice. Thus, lack of SGK1 does not disrupt colonic ENaC activity and its regulation by salt depletion.