Evan C Ray, Andrew Nickerson, Shaohu Sheng, Rolando Carrisoza-Gaytan, 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 gamma subunit is essential for homeostasis of Na + , K + , and body fluid. Dual subunit cleavage before and after a short inhibitory tract allows dissociation of this tract, increasing channel open probability (P O ), in vitro . Cleavage proximal to the tract occurs at a furin recognition sequence ( 143 RKRR 146 in mouse). Loss of furin-mediated cleavage prevents in vitro activation of the channel by proteolysis at distal sites. We hypothesized that 143 RKRR 146 mutation to 143 QQQQ 146 ( Q4 ) in 129/Sv mice would reduce ENaC P O , impair flow-stimulated flux of Na + (J Na ) and K + (J K ) in perfused collecting ducts, reduce colonic amiloride-sensitive short circuit current (I SC ), and impair Na + , K + , and body fluid homeostasis...
February 14, 2024: bioRxiv