A growing body of evidence suggests that the extracellular domain of the epithelial Na+
channel (ENaC) functions as a sensor that fine tunes channel activity in response to
changes in the extracellular environment. We previously found that acidic pH increases the
activity of human ENaC, which results from a decrease in Na+ self-inhibition. In the current
work, we identified extracellular domain residues responsible for this regulation. We found
that rat ENaC is less sensitive to pH than human ENaC, an effect mediated in part by the γ …