ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Deletion of the GABA(A) receptor alpha1 subunit increases tonic GABA(A) receptor current: a role for GABA uptake transporters.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. 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, 62 citations in OpenAlex.
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- Effect of cortical extracellular GABA on motor response.Journal of computational neuroscience · 2022Article
- NKCC1, an Elusive Molecular Target in Brain Development: Making Sense of the Existing Data.Cells · 2020Review
- Gain-of-functionBrain communications · 2020Article
- Reducing variability in motor cortex activity at a resting state by extracellular GABA for reliable perceptual decision-making.Journal of computational neuroscience · 2019Article
- Role of cerebellar GABAergic dysfunctions in the origins of essential tremor.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Perinatal high-fat diet alters development of GABAAmerican journal of physiology. Gastrointestinal and liver physiology · 2019Article
- MMP-1 overexpression selectively alters inhibition in D1 spiny projection neurons in the mouse nucleus accumbens core.Scientific reports · 2018Article
- Differential electrophysiological properties of D1 and D2 spiny projection neurons in the mouse nucleus accumbens core.Physiological reports · 2018Article
- Neuregulin 3 Signaling Mediates Nicotine-Dependent Synaptic Plasticity in the Orbitofrontal Cortex and Cognition.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Perinatal high fat diet increases inhibition of dorsal motor nucleus of the vagus neurons regulating gastric functions.Neurogastroenterology and motility · 2018Article
- Differential Modulation of GABAFrontiers in molecular neuroscience · 2017Article
- GPR30 disrupts the balance of GABAergic and glutamatergic transmission in the spinal cord driving to the development of bone cancer pain.Oncotarget · 2016Article
- Linking Essential Tremor to the Cerebellum-Animal Model Evidence.Cerebellum (London, England) · 2016Review
- Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure.Journal of neurophysiology · 2015Article
- Modulation of the input-output function by GABAA receptor-mediated currents in rat oculomotor nucleus motoneurons.The Journal of physiology · 2014Article
- GABAA receptor-mediated tonic depolarization in developing neural circuits.Molecular neurobiology · 2014Review
- Comparison of mibefradil and derivative NNC 55-0396 effects on behavior, cytochrome P450 activity, and tremor in mouse models of essential tremor.European journal of pharmacology · 2011Article
- Augmentation of Tonic GABA(A) Inhibition in Absence Epilepsy: Therapeutic Value of Inverse Agonists at Extrasynaptic GABA(A) Receptors.Advances in pharmacological sciences · 2011Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The loss of more than half the number of GABA(A) receptors yet lack of pronounced phenotype in mice lacking the gene for the GABA(A) alpha1 subunit is somewhat paradoxical. We explored the role of tonic GABA(A) receptor-mediated current as a target of compensatory regulation in the alpha1 knock-out (-/-) mice. A 62% increase of tonic current was observed in the cerebellar granule cells (CGCs) of alpha1-/- compared with wild-type (+/+) mice along with a 67% increase of baseline current variance. Examination of whole-cell currents evoked by low concentrations of GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol suggested no upregulation of alpha6 and delta subunit-containing GABA(A) receptors in the alpha1-/-, confirming previous biochemical studies. Single-channel current openings were on average 32% shorter in the alpha1-/- neurons. Single-channel conductance and frequency of opening were not different between genotypes. Tonic current induced by application of the GABA transporter GAT-1 blocker NO711 (1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride) was significantly larger in the alpha1-/-, suggesting an increase of ambient GABA concentration. Experiments done with a known concentration of extracellular GABA complemented by a series of biochemical experiments revealed a reduction of GAT activity in alpha1-/- without an identifiable reduction of GAT-1 or GAT-3 protein. We report increased tonic GABA(A) receptor-mediated current in the alpha1-/- CGCs as a novel compensatory mechanism. Our data establish a role for GABA transporters as regulators of neuronal excitability in this and relevant models and examine other tonic conductance-regulating mechanisms responsible for the adaptive response of the cerebellar network to a deletion of a major synaptic GABA(A) receptor subunit.
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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.