ArticlePflugers Archiv : European journal of physiology2005
Endogenous RGS proteins enhance acute desensitization of GABA(B) receptor-activated GIRK currents in HEK-293T cells.
Article in Pflugers Archiv : European journal of physiology, 2005. 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, 53 citations in OpenAlex.
- A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.Nature communications · 2024Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.bioRxiv : the preprint server for biology · 2024Article
- Gain-of-function KCNJ6 Mutation in a Severe Hyperkinetic Movement Disorder Phenotype.Neuroscience · 2018Article
- Diversity of structure and function of GABAProceedings of the Japan Academy. Series B, Physical and biological sciences · 2018Review
- KCTD Hetero-oligomers Confer Unique Kinetic Properties on Hippocampal GABAB Receptor-Induced K+ Currents.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- GABAB receptor phosphorylation regulates KCTD12-induced K⁺ current desensitization.Biochemical pharmacology · 2014Article
- Short-term desensitization of muscarinic K+ current in the heart.Biophysical journal · 2013Article
- Opposite effects of KCTD subunit domains on GABA(B) receptor-mediated desensitization.The Journal of biological chemistry · 2012Article
- Baclofen administration alters fear extinction and GABAergic protein levels.Neurobiology of learning and memory · 2012Article
- Regulation of neuronal GABA(B) receptor functions by subunit composition.Nature reviews. Neuroscience · 2012Review
- Modulation of cell surface GABA(B) receptors by desensitization, trafficking and regulated degradation.World journal of biological chemistry · 2012Article
- In vivo ethanol experience increases D(2) autoinhibition in the ventral tegmental area.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2011Article
- The GABAβ receptor as a target for antidepressant drug action.British journal of pharmacology · 2011Review
- Plasticity of postsynaptic, but not presynaptic, GABAB receptors in SSADH deficient mice.Experimental neurology · 2010Article
- R4 RGS proteins: regulation of G-protein signaling and beyond.Pharmacology & therapeutics · 2007Review
- Coregulation of natively expressed pertussis toxin-sensitive muscarinic receptors with G-protein-activated potassium channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
- Evidence for association of GABA(B) receptors with Kir3 channels and regulators of G protein signalling (RGS4) proteins.The Journal of physiology · 2007Article
- Active Galpha(q) subunits and M3 acetylcholine receptors promote distinct modes of association of RGS2 with the plasma membrane.FEBS letters · 2007Article
- Distinct populations of spinal cord lamina II interneurons expressing G-protein-gated potassium channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- Molecular and cellular diversity of neuronal G-protein-gated potassium channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The coupling of GABA(B) receptors to G-protein-gated inwardly rectifying potassium (GIRK) channels constitutes an important inhibitory pathway in the brain. Here, we examined the mechanism underlying desensitization of agonist-evoked currents carried by homomeric GIRK2 channels expressed in HEK-293T cells. The canonical GABA(B) receptor agonist baclofen produced GIRK2 currents that decayed by 57.3+/-1.4% after 60 s of stimulation, and then deactivated rapidly (time constant of 3.90+/-0.21 s) upon removal of agonist. Surface labeling studies revealed that GABA(B) receptors, in contrast to micro opioid receptors (MOR), did not internalize with a sustained stimulation for 10 min, excluding receptor redistribution as the primary mechanism for desensitization. Furthermore, heterologous desensitization was observed between GABA(B) receptors and MOR, implicating downstream proteins, such G-proteins or the GIRK channel. To investigate the G-protein turnover cycle, the non-hydrolyzable GTP analogue (GTPgammaS) was included in the intracellular solution and found to attenuate desensitization to 38.3+/-2.0%. The extent of desensitization was also reduced (45.3+/-1.3%) by coexpressing a mutant form of the Galphaq G-protein subunit that has been designed to sequester endogenous RGS proteins. Finally, reconstitution of GABA(B) receptors with Galphao G-proteins rendered insensitive to RGS resulted in significantly less desensitization (28.5+/-3.2%). Taken together, our results demonstrate that endogenous levels of RGS proteins effectively enhance GABA(B) receptor-dependent desensitization of GIRK currents.
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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.