Altering intracellular pH reveals the kinetic basis of intraburst gating in the CFTR Cl− channel

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12084-list-0001">The cystic fibrosis transmembrane conductance regulator (CFTR), which is defective in the genetic disease cystic fibrosis (CF), forms a gated pathway for chloride movement regulated by intracellular ATP.To understand better CFTR function, we investigated the regulation of channel openings by intracellular pH.We found that short‐lived channel closures during channel openings represent subtle changes in the structure of CFTR that are regulated by intracellular pH, in part, at ATP‐binding site 1 formed by the nucleotide‐binding domains.Our results provide a framework for future studies to understand better the regulation of channel openings, the dysfunction of CFTR in CF and the action of drugs that repair CFTR gating defects.