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Updated: Aug 29, 2026

Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
Published on: March 9, 2015
Altered channel gating mechanism for CFTR inhibition by a high-affinity thiazolidinone blocker
Alessandro Taddei1, Chiara Folli, Olga Zegarra-Moran
1Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, 16148 Genoa, Italy.
Abstract:
The thiazolidinone CFTR(inh)-172 was identified recently as a potent and selective blocker of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Here, we characterized the CFTR(inh)-172 inhibition mechanism by patch-clamp and short-circuit analysis using cells stably expressing wild-type and mutant CFTRs. CFTR(inh)-172 did not alter CFTR unitary conductance (8 pS), but reduced open probability by >90% with K(i) approximately 0.6 microM. This effect was due to increased mean channel closed time without changing mean channel open time. Short-circuit current experiments indicated similar CFTR(inh)-172 inhibitory potency (K(i) approximately 0.5 microM) for inhibition of Cl(-) current in wild-type, G551D, and G1349D CFTR; however, K(i) was significantly reduced to 0.2 microM for DeltaF508 CFTR. Our studies provide evidence for CFTR inhibition by CFTR(inh)-172 by a mechanism involving altered CFTR gating.
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