ArticleThe Journal of general physiology2008
Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors.
Article in The Journal of general physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- State-dependent energetics of GABABiophysical journal · 2024Article
- Shisa7-Dependent Regulation of GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Discovery of a new class of orthosteric antagonists with nanomolar potency at extrasynaptic GABAScientific reports · 2020Article
- Steady-state activation of the high-affinity isoform of the α4β2δ GABAScientific reports · 2019Article
- Reconstitution of Human Ion Channels into Solvent-free Lipid Bilayers Enhanced by Centrifugal Forces.Biophysical journal · 2016Article
- A nonequilibrium binary elements-based kinetic model for benzodiazepine regulation of GABAA receptors.The Journal of general physiology · 2014Article
- GABAA receptor α and γ subunits shape synaptic currents via different mechanisms.The Journal of biological chemistry · 2014Article
- Homeostatic competition between phasic and tonic inhibition.The Journal of biological chemistry · 2013Article
- The natural products magnolol and honokiol are positive allosteric modulators of both synaptic and extra-synaptic GABA(A) receptors.Neuropharmacology · 2012Article
- Stoichiometry of expressed alpha(4)beta(2)delta gamma-aminobutyric acid type A receptors depends on the ratio of subunit cDNA transfected.The Journal of biological chemistry · 2010Article
- Distinct activities of GABA agonists at synaptic- and extrasynaptic-type GABAA receptors.The Journal of physiology · 2010Article
- Modulation of spontaneous and GABA-evoked tonic alpha4beta3delta and alpha4beta3gamma2L GABAA receptor currents by protein kinase A.Journal of neurophysiology · 2010Article
- The activation mechanism of alpha1beta2gamma2S and alpha3beta3gamma2S GABAA receptors.The Journal of general physiology · 2010Article
- An epilepsy-related region in the GABA(A) receptor mediates long-distance effects on GABA and benzodiazepine binding sites.Molecular pharmacology · 2010Article
- Long-range coupling in an allosteric receptor revealed by mutant cycle analysis.Biophysical journal · 2009Article
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Abstract
The family of gamma-aminobutyric acid type A receptors (GABA(A)Rs) mediates two types of inhibition in the mammalian brain. Phasic inhibition is mediated by synaptic GABA(A)Rs that are mainly comprised of alpha(1), beta(2), and gamma(2) subunits, whereas tonic inhibition is mediated by extrasynaptic GABA(A)Rs comprised of alpha(4/6), beta(2), and delta subunits. We investigated the activation properties of recombinant alpha(4)beta(2)delta and alpha(1)beta(2)gamma(2S) GABA(A)Rs in response to GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one (THIP) using electrophysiological recordings from outside-out membrane patches. Rapid agonist application experiments indicated that THIP produced faster opening rates at alpha(4)beta(2)delta GABA(A)Rs (beta approximately 1600 s(-1)) than at alpha(1)beta(2)gamma(2S) GABA(A)Rs (beta approximately 460 s(-1)), whereas GABA activated alpha(1)beta(2)gamma(2S) GABA(A)Rs more rapidly (beta approximately 1800 s(-1)) than alpha(4)beta(2)delta GABA(A)Rs (beta < 440 s(-1)). Single channel recordings of alpha(1)beta(2)gamma(2S) and alpha(4)beta(2)delta GABA(A)Rs showed that both channels open to a main conductance state of approximately 25 pS at -70 mV when activated by GABA and low concentrations of THIP, whereas saturating concentrations of THIP elicited approximately 36 pS openings at both channels. Saturating concentrations of GABA elicited brief (<10 ms) openings with low intraburst open probability (P(O) approximately 0.3) at alpha(4)beta(2)delta GABA(A)Rs and at least two "modes" of single channel bursting activity, lasting approximately 100 ms at alpha(1)beta(2)gamma(2S) GABA(A)Rs. The most prevalent bursting mode had a P(O) of approximately 0.7 and was described by a reaction scheme with three open and three shut states, whereas the "high" P(O) mode ( approximately 0.9) was characterized by two shut and three open states. Single channel activity elicited by THIP in alpha(4)beta(2)delta and alpha(1)beta(2)gamma(2S) GABA(A)Rs occurred as a single population of bursts (P(O) approximately 0.4-0.5) of moderate duration (approximately 33 ms) that could be described by schemes containing two shut and two open states for both GABA(A)Rs. Our data identify kinetic properties that are receptor-subtype specific and others that are agonist specific, including unitary conductance.
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