Intracellular H+ regulates the α-subunit of ENaC, the epithelial Na+ channel

• DOI: 10.1152/ajpcell.1999.276.2.c477
• Publication Date: 2017-12-24T22:24:23Z
• Authors: Michael L. Chalfant; Jerod S. Denton; Bakhram K. Berdiev; Iskander I. Ismailov; Dale J. Benos; Bruce A. Stanton
• Keywords: Epithelial sodium channel; Apical membrane

Protons regulate electrogenic sodium absorption in a variety of epithelia, including the cortical collecting duct, frog skin, and urinary bladder. Recently, three subunits (α, β, γ) coding for epithelial channel (ENaC) were cloned. However, it is not known whether pH regulates Na + channels directly by interacting with one ENaC or indirectly regulatory protein. As first step to identifying molecular mechanisms proton-mediated regulation apical membrane permeability we examined effect on biophysical properties ENaC. To this end, expressed various combinations α-, β-, γ-subunits Xenopusoocytes studied currents two-electrode voltage-clamp patch-clamp techniques. In addition, α-ENaC subunit was planar lipid bilayers. We report that α,β,γ-ENaC regulated changes intracellular (pH i ) but extracellular o ). Acidification reduced alkalization increased activity voltage-independent mechanism. Moreover, reduction single-channel open probability, time, closed time without altering conductance. cytoplasmic solution also inhibited α,β-ENaC, α,γ-ENaC, currents. conclude .