Maximization of the rate of chloride conduction in the CFTR channel pore by ion–ion interactions

Multi-ion pore behaviour has been identified in many Cl− channel types but its biophysical significance is uncertain. Here, we show that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel that disrupt anion–anion interactions within the pore are associated with drastically reduced single channel conductance. These results are consistent with models suggesting that rapid Cl− permeation in CFTR results from repulsive ion–ion interactions between Cl− ions bound concurrently inside the pore. Naturally occurring mutations that disrupt these interactions can result in cystic fibrosis.