ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Modulation of GABA(A) receptors by hydrogen ions reveals synaptic GABA transient and a crucial role of the desensitization process.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
56 citing papers in PubMed, 113 citations in OpenAlex.
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- The regulatory role of GABAPflugers Archiv : European journal of physiology · 2021Article
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- Decreased Brain pH and Pathophysiology in Schizophrenia.International journal of molecular sciences · 2021Review
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- Characterization of zebrafish GABAScientific reports · 2021Article
- Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle.Nature communications · 2020Article
- Nanoscale Subsynaptic Domains Underlie the Organization of the Inhibitory Synapse.Cell reports · 2019Article
- Methylene blue inhibits GABANeuropharmacology · 2017Article
- Acute inflammation reveals GABAPhysiological reports · 2017Article
- The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus.Frontiers in neuroendocrinology · 2017Review
- Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition.The Journal of physiology · 2014Article
Corrections and comments
- Erratum issuedZarmowska, E D [corrected to Zarnowska, E D]
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protons are the most ubiquitous and very potent modulators of the biological systems. Hydrogen ions are known to modulate GABA(A) receptors (GABA(A)Rs), but the mechanism whereby these ions affect IPSCs and the gating of GABA(A)Rs is not clear. In the present study we examined the effect of protons on miniature IPSCs (mIPSCs) and found that hydrogen ions strongly affected both their amplitude and time course. To explore the underlying mechanisms with resolution adequate to the time scale of synaptic transmission, we recorded current responses to ultrafast GABA applications at various pH. These experiments revealed that the major effect of protons on GABA(A)R gating is a strong enhancement of desensitization and binding rates at increasing pH. This analysis also indicated that desensitization rate is the fastest ligand-independent transition in the GABA(A)R gating scheme. Although proton effects on the time course of mIPSCs and current responses to saturating [GABA] were similar, the pH dependencies of amplitudes were almost opposite. Our quantitative analysis, based on model simulations, indicated that this difference resulted from a much shorter receptor exposure to agonist in the case of mIPSCs. Modeling of IPSCs as current responses to brief exponentially decaying GABA applications was sufficient to reproduce correctly the pH dependence of mIPSCs, and optimal fit was obtained for peak [GABA] of 1.5-3 mm and a clearance time constant of 0.075-0.125 msec. Our analysis indicates that, for these parameters of GABA transient, in control conditions (pH 7.2) mIPSCs are not saturated.
Indexed as
Identifiers
12954859PMC6740496W2114658217What OpenQuestion holds
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.