ArticleThe Journal of physiology2002
Conformation-dependent regulation of inward rectifier chloride channel gating by extracellular protons.
Article in The Journal of physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
- The loss of a ClC anion channel increases life span, health span, and stress resistance by alkalinizing a pair of glial cells inScience advances · 2025Article
- Article
- CryoEM structures of the human CLC-2 voltage gated chloride channel reveal a ball and chain gating mechanism.bioRxiv : the preprint server for biology · 2023Article
- Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.Nature communications · 2023Article
- A glial ClC ClNeuron · 2022Article
- Electro-steric opening of the CLC-2 chloride channel gate.Scientific reports · 2021Article
- Glial Chloride Channels in the Function of the Nervous System Across Species.Advances in experimental medicine and biology · 2021Article
- Effects of the Tumor Environment on Ion Channels: Implication for Breast Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Extracellular protons enable activation of the calcium-dependent chloride channel TMEM16A.The Journal of physiology · 2017Article
- Gating the glutamate gate of CLC-2 chloride channel by pore occupancy.The Journal of general physiology · 2016Article
- Regulatory-auxiliary subunits of CLC chloride channel-transport proteins.The Journal of physiology · 2015Review
- The principal conductance in Giardia lamblia trophozoites possesses functional properties similar to the mammalian ClC-2 current.Pflugers Archiv : European journal of physiology · 2014Article
- Alkaline pH block of CLC-K kidney chloride channels mediated by a pore lysine residue.Biophysical journal · 2013Article
- Ion channels in renal disease.Chemical reviews · 2012Review
- Sequential interaction of chloride and proton ions with the fast gate steer the voltage-dependent gating in ClC-2 chloride channels.The Journal of physiology · 2012Article
- A regulatory calcium-binding site at the subunit interface of CLC-K kidney chloride channels.The Journal of general physiology · 2010Article
- Permeant anions contribute to voltage dependence of ClC-2 chloride channel by interacting with the protopore gate.The Journal of physiology · 2010Article
- Functional characterization of a ClC-2-like Cl(-) conductance in surface epithelial cells of rat rectal colon.The Journal of membrane biology · 2010Article
- Inward-rectifier chloride currents in Reissner's membrane epithelial cells.Biochemical and biophysical research communications · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We have investigated the gating properties of the inward rectifier chloride channel (Cl(ir)) from mouse parotid acinar cells by external protons (H(+)(o)) using the whole-cell patch-clamp technique. Increasing the pH(o) from 7.4 to 8.0 decreased the magnitude of Cl(ir) current by shifting the open probability to more negative membrane potentials with little modification of the activation kinetics. The action of elevated pH was independent of the conformational state of the channel. The effects of low pH on Cl(ir) channels were dependent upon the conformational state of the channel. That is, application of pH 5.5 to closed channels essentially prevented channel opening. In contrast, application of pH 5.5 to open channels actually increased the current. These results are consistent with the existence of two independent protonatable sites: (1) a site with a pK near 7.3, the titration of which shifts the voltage dependence of channel gating; and (2) a site with pK = 6.0. External H(+) binds to this latter site (with a stoichiometry of two) only when the channels are closed and prevent channel opening. Finally, block of channels by Zn(2+) and Cd(2+) was inhibited by low pH media. We propose that mouse parotid Cl(ir) current has a bimodal dependence on the extracellular proton concentration with maximum activity near pH 6.5: high pH decreases channel current by shifting the open probability to more negative membrane potentials and low pH also decreases the current but through a proton-dependent stabilization of the channel closed state.
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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.