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 mug/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.