ArticleBritish journal of pharmacology2002
Mechanism of lonidamine inhibition of the CFTR chloride channel.
Article in British journal of pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 35 citations in OpenAlex.
- The lonidamine derivative H2-gamendazole reduces cyst formation in polycystic kidney disease.American journal of physiology. Renal physiology · 2022Article
- Structural mechanisms of CFTR function and dysfunction.The Journal of general physiology · 2018Review
- Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, biophysical and physiological relevance.World journal of biological chemistry · 2014Review
- Loop diuretics are open-channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics.British journal of pharmacology · 2014Article
- Divergent CFTR orthologs respond differently to the channel inhibitors CFTRinh-172, glibenclamide, and GlyH-101.American journal of physiology. Cell physiology · 2012Article
- Regulation of conductance by the number of fixed positive charges in the intracellular vestibule of the CFTR chloride channel pore.The Journal of general physiology · 2010Article
- Direct and indirect effects of mutations at the outer mouth of the cystic fibrosis transmembrane conductance regulator chloride channel pore.The Journal of membrane biology · 2007Article
- On the origin of asymmetric interactions between permeant anions and the cystic fibrosis transmembrane conductance regulator chloride channel pore.Biophysical journal · 2007Article
- Interactions between impermeant blocking ions in the cystic fibrosis transmembrane conductance regulator chloride channel pore: evidence for anion-induced conformational changes.The Journal of membrane biology · 2006Article
- Mutation-induced blocker permeability and multiion block of the CFTR chloride channel pore.The Journal of general physiology · 2003Article
- Coupled movement of permeant and blocking ions in the CFTR chloride channel pore.The Journal of physiology · 2003Article
- Molecular determinants and role of an anion binding site in the external mouth of the CFTR chloride channel pore.The Journal of physiology · 2003Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is blocked by a broad range of organic anionic compounds. Here we investigate the effects of the indazole compound lonidamine on CFTR channels expressed in mammalian cell lines using patch clamp recording. 2. Application of lonidamine to the intracellular face of excised membrane patches caused a voltage-dependent block of CFTR currents, with an apparent K(d) of 58 micro M at -100 mV. 3. Block by lonidamine was apparently independent of channel gating but weakly sensitive to the extracellular Cl(-) concentration. 4. Intracellular lonidamine led to the introduction of brief interruptions in the single channel current at hyperpolarized voltages, leading to a reduction in channel mean open time. Lonidamine also introduced a new component of macroscopic current variance. Spectral analysis of this variance suggested a blocker on rate of 1.79 micro M(-1) s(-1) and an off-rate of 143 s(-1). 5. Several point mutations within the sixth transmembrane region of CFTR (R334C, F337S, T338A and S341A) significantly weakened block of macroscopic CFTR current, suggesting that lonidamine enters deeply into the channel pore from its intracellular end. 6. These results identify and characterize lonidamine as a novel CFTR open channel blocker and provide important information concerning its molecular mechanism of action.
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