ArticleThe Journal of general physiology1997
Tetracaine reports a conformational change in the pore of cyclic nucleotide-gated channels.
Article in The Journal of general physiology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- CNG channel structure, function, and gating: a tale of conformational flexibility.Pflugers Archiv : European journal of physiology · 2021Review
- Mechanism of ligand activation of a eukaryotic cyclic nucleotide-gated channel.Nature structural & molecular biology · 2020Article
- Closed state-coupled C-type inactivation in BK channels.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Paxilline inhibits BK channels by an almost exclusively closed-channel block mechanism.The Journal of general physiology · 2014Article
- cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.PloS one · 2014Article
- A ring of threonines in the inner vestibule of the pore of CNGA1 channels constitutes a binding site for permeating ions.The Journal of physiology · 2012Article
- Halogen substituents on the aromatic moiety of the tetracaine scaffold improve potency of cyclic nucleotide-gated channel block.Bioorganic & medicinal chemistry letters · 2011Article
- Cyclic nucleotide-gated channel block by hydrolysis-resistant tetracaine derivatives.Journal of medicinal chemistry · 2011Article
- Article
- Mutations reveal voltage gating of CNGA1 channels in saturating cGMP.The Journal of general physiology · 2009Article
- Discovery of potent CLC chloride channel inhibitors.ACS chemical biology · 2008Article
- A comparison of electrophysiological properties of the CNGA1, CNGA1tandem and CNGA1cys-free channels.European biophysics journal : EBJ · 2008Article
- Gating at the selectivity filter in cyclic nucleotide-gated channels.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Block of cyclic nucleotide-gated channels by tetracaine derivatives: role of apolar interactions at two distinct locations.Bioorganic & medicinal chemistry letters · 2008Article
- State-independent block of BK channels by an intracellular quaternary ammonium.The Journal of general physiology · 2006Article
- Access of quaternary ammonium blockers to the internal pore of cyclic nucleotide-gated channels: implications for the location of the gate.The Journal of general physiology · 2006Article
- The pharmacology of cyclic nucleotide-gated channels: emerging from the darkness.Current pharmaceutical design · 2006Review
- Modifications to the tetracaine scaffold produce cyclic nucleotide-gated channel blockers with widely varying efficacies.Journal of medicinal chemistry · 2005Article
- Mutation of the pore glutamate affects both cytoplasmic and external dequalinium block in the rat olfactory CNGA2 channel.European biophysics journal : EBJ · 2005Article
- Probing the pore of the auditory hair cell mechanotransducer channel in turtle.The Journal of physiology · 2004Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Local anesthetics are a diverse group of clinically useful compounds that act as pore blockers of both voltage- and cyclic nucleotide-gated (CNG) ion channels. We used the local anesthetic tetracaine to probe the nature of the conformational change that occurs in the pore of CNG channels during the opening allosteric transition. When applied to the intracellular side of wild-type rod CNG channels expressed in Xenopus oocytes from the alpha subunit, the local anesthetic tetracaine exhibits state-dependent block, binding with much higher affinity to closed states than to open states. Here we show that neutralization of a glutamic acid in the conserved P region (E363G) eliminated this state dependence of tetracaine block. Tetracaine blocked E363G channels with the same effectiveness at high concentrations of cGMP, when the channel spent more time open, and at low concentrations of cGMP, when the channel spent more time closed. In addition, Ni2+, which promotes the opening allosteric transition, decreased the effectiveness of tetracaine block of wild-type but not E363G channels. Similar results were obtained in a chimeric CNG channel that exhibits a more favorable opening allosteric transition. These results suggest that E363 is accessible to internal tetracaine in the closed but not the open configuration of the pore and that the conformational change that accompanies channel opening includes a change in the conformation or accessibility of E363.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.