Mechanistic target of rapamycin complex-1 (mTORc1) plays a role in inhibiting kidney K ⁺ excretion during overnight dietary K ⁺ restriction

Decreased dietary K + -intake stimulates the expression of Regulatory-Associated-Protein-of-mTOR (RAPTOR) in kidneys and increases mRNA of Raptor in aldosterone sensitive distal nephrons. The aim of the study is to explore the role of mTORc1 in stimulating Kir4.1/Kir5.1 and Na-Cl-cotransporter (NCC), and inhibiting renal-outer-medullary K + channel (ROMK or Kir1.1) and epithelial-Na + -channel (ENaC) during overnight low-K + -intake (LK). Deletion of RAPTOR in kidneys inhibited basolateral Kir4.1/Kir5.1 of distal convoluted tubule (DCT) and decreased the expression of phosphor-NCC and total-NCC. Furthermore, ENaC and ROMK baseline activity in late-DCT/early connecting tubule (CNT) and cortical collecting duct (CCD) of kidney-tubule-specific-RAPTOR knockout mice (Ks-RAPTOR-KO) were higher than Raptor flox/flox mice. Consequently, Ks-RAPTOR-KO mice had higher baseline kidney K + excretion and lower plasma K + concentrations than Raptor flox/flox mice. Overnight-LK-intake stimulated Kir4.1/Kir5.1 activity of DCT and the expression of phosphor-NCC and total-NCC in Raptor flox/flox mice. In contrast, overnight-LK failed to stimulate Kir4.1/Kir5.1 of the DCT and did not increase the expression of phosphor-NCC and total-NCC in Ks-RAPTOR-KO mice. Moreover, overnight-LK inhibits ROMK and ENaC in late-DCT/early-CNT and CCD only in Raptor flox/flox mice but not in Ks-RAPTOR-KO mice. Thus, male/female Ks-RAPTOR-KO mice on overnight-LK had lower plasma K + levels and higher kidney K + excretion than Raptor flox/flox mice. We conclude that mTORc1 plays a key role in suppressing kidney K + excretion during decreased dietary K + intake.