ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2001
Dominant gating governing transient GABA(A) receptor activity: a first latency and Po/o analysis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
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- Exploring the mechanism of general anesthesia: kinetic analysis of GABAA receptor electrophysiology.Biophysical journal · 2015Article
- Cysteine substitutions define etomidate binding and gating linkages in the α-M1 domain of γ-aminobutyric acid type A (GABAA) receptors.The Journal of biological chemistry · 2013Article
- An outline of desensitization in pentameric ligand-gated ion channel receptors.Cellular and molecular life sciences : CMLS · 2013Review
- A state-dependent salt-bridge interaction exists across the β/α intersubunit interface of the GABAA receptor.Molecular pharmacology · 2011Article
- Kinetic analysis of evoked IPSCs discloses mechanism of antagonism of synaptic GABAA receptors by picrotoxin.British journal of pharmacology · 2010Article
- Pentobarbital produces activation and block of {alpha}1{beta}2{gamma}2S GABAA receptors in rapidly perfused whole cells and membrane patches: divergent results can be explained by pharmacokinetics.The Journal of general physiology · 2009Article
- Microscopic kinetic determinants of macroscopic currents: insights from coupling and uncoupling of GABAA receptor desensitization and deactivation.The Journal of physiology · 2007Article
- Ethanol effects on GABA-gated current in a model of increased alpha4betadelta GABAA receptor expression depend on time course and preexposure to low concentrations of the drug.Alcohol (Fayetteville, N.Y.) · 2007Article
- The pre-M1 segment of the alpha1 subunit is a transduction element in the activation of the GABAA receptor.The Journal of physiology · 2006Article
- Modes and models of GABA(A) receptor gating.The Journal of physiology · 2006Article
- Tandem subunits effectively constrain GABAA receptor stoichiometry and recapitulate receptor kinetics but are insensitive to GABAA receptor-associated protein.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
- Neurosteroid administration and withdrawal alter GABAA receptor kinetics in CA1 hippocampus of female rats.The Journal of physiology · 2005Article
- Use of the covariance matrix in directly fitting kinetic parameters: application to GABAA receptors.Biophysical journal · 2004Article
- Neuroactive steroids have multiple actions to potentiate GABAA receptors.The Journal of physiology · 2004Article
- Activation of single heteromeric GABA(A) receptor ion channels by full and partial agonists.The Journal of physiology · 2004Article
- An arginine involved in GABA binding and unbinding but not gating of the GABA(A) receptor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2004Article
- Kinetic properties of the alpha2 homo-oligomeric glycine receptor impairs a proper synaptic functioning.The Journal of physiology · 2003Article
- Modulation of GABA(A) receptors by hydrogen ions reveals synaptic GABA transient and a crucial role of the desensitization process.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003Article
- Coupled and uncoupled gating and desensitization effects by pore domain mutations in GABA(A) receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2002Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Steady-state, single-channel gating of GABA(A) receptors (GABARs ) is complex. Simpler gating may dominate when triggered by rapid GABA transients present during fast inhibitory synaptic transmission and is critical to understanding the time course of fast IPSCs. We studied the single-channel activity of expressed alpha1beta1gamma2 GABARs in outside-out patches from human embryonic kidney 293 cells triggered by rapidly applied GABA (10-2000 microm) pulses (2-300 msec). Activation was analyzed with the time to first channel opening after GABA presentation, or first latency (FL). FL distributions are monoexponential at low GABA concentrations and biexponential above 30 microm GABA. The fast rate increases supralinearly to a plateau of approximately 1100 sec(-1), the apparent activation rate. The slow rate and amplitude are insensitive to GABA concentration. The results argue that doubly liganded receptors can rapidly desensitize before opening. Gating after the first opening was quantified with analysis of open probability conditioned on the first opening (P(o/o)). P(o/o) functions are biexponential, dominated by a fast component, and insensitive to GABA concentration. This suggests that open channels convert primarily to fast but also to slow desensitized states. Furthermore, dual modes of fast desensitization may influence IPSC amplitude and thereby synaptic efficacy. The findings provided for the construction of a mathematical gating model that accounts for FL and P(o/o) functions. In addition, the model predicts the time course of macroscopic current responses thought to mimic IPSCs. The results provide new insights into dominant gating that is likely operational during fast GABAergic synaptic transmission.
Indexed as
Identifiers
11549712PMC6762978W2141639867What 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.