Evan C Ray, Andrew Nickerson, Shaohu Sheng, Rolando Carrisoza-Gaytán, Tracey Lam, Allison Marciszyn, Lei Zhang, Alexa Jordahl, Chunming Bi, Aaliyah Winfrey, Zhaohui Kou, Sebastien Gingras, Annet Kirabo, Lisa M Satlin, Thomas R Kleyman
The ENaC γ subunit is essential for homeostasis of Na+ , K+ , and body fluid. Dual γ subunit cleavage before and after a short inhibitory tract allows dissociation of this tract, increasing channel open probability (PO ), in vitro . Cleavage proximal to the tract occurs at a furin recognition sequence (143 RKRR146 , in the mouse γ subunit). Loss of furin-mediated cleavage prevents in vitro activation of the channel by proteolysis at distal sites. We hypothesized that 143 RKRR146 mutation to 143 QQQQ146 (γQ4 ) in 129/Sv mice would reduce ENaC PO , impair flow-stimulated flux of Na+ (JNa ) and K+ (JK ) in perfused collecting ducts, reduce colonic amiloride-sensitive short circuit current (ISC ), and impair Na+ , K+ , and body fluid homeostasis...
April 18, 2024: American Journal of Physiology. Renal Physiology