ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Cell type-specific differences in chloride-regulatory mechanisms and GABA(A) receptor-mediated inhibition in rat substantia nigra.
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. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 126 citations in OpenAlex.
- Midbrain KCC2 downregulation: Implications for stress-related and substance use behaviors.Current opinion in neurobiology · 2024Review
- Impact of Unitary Synaptic Inhibition on Spike Timing in Ventral Tegmental Area Dopamine Neurons.eNeuro · 2024Article
- Expression patterns of NKCC1 in neurons and non-neuronal cells during cortico-hippocampal development.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Evaluation of bumetanide as a potential therapeutic agent for Alzheimer's disease.Frontiers in pharmacology · 2023Review
- Dendritic involvement in inhibition and disinhibition of vulnerable dopaminergic neurons in healthy and pathological conditions.Neurobiology of disease · 2022Review
- Striatonigrostriatal circuit architecture for disinhibition of dopamine signaling.Cell reports · 2022Article
- Striatal Chloride Dysregulation and Impaired GABAergic Signaling Due to Cation-Chloride Cotransporter Dysfunction in Huntington's Disease.Frontiers in cellular neuroscience · 2021Review
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- Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization.Nature communications · 2020Article
- TGF-β/Smad3 Signalling Modulates GABA Neurotransmission: Implications in Parkinson's Disease.International journal of molecular sciences · 2020Review
- Predicting responses to inhibitory synaptic input in substantia nigra pars reticulata neurons.Journal of neurophysiology · 2018Article
- Adolescent Nicotine Exposure Alters GABACell reports · 2018Article
- Convergent Neuronal Plasticity and Metaplasticity Mechanisms of Stress, Nicotine, and Alcohol.Annual review of pharmacology and toxicology · 2018Review
- Research and progress on ClC‑2 (Review).Molecular medicine reports · 2017Review
- Dopamine Inhibition Differentially Controls Excitability of Substantia Nigra Dopamine Neuron Subpopulations through T-Type Calcium Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.Trends in pharmacological sciences · 2016Review
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- Neuroimmune Regulation of GABAergic Neurons Within the Ventral Tegmental Area During Withdrawal from Chronic Morphine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Transient Activation of GABAB Receptors Suppresses SK Channel Currents in Substantia Nigra Pars Compacta Dopaminergic Neurons.PloS one · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The regulation of intracellular chloride has important roles in neuronal function, especially by setting the magnitude and direction of the Cl- flux gated by GABA(A) receptors. Previous studies have shown that GABA(A)-mediated inhibition is less effective in dopaminergic than in GABAergic neurons in substantia nigra. We studied whether this phenomenon may be related to a difference in Cl-regulatory mechanisms. Light-microscopic immunocytochemistry revealed that the potassium-chloride cotransporter 2 (KCC2) was localized only in the dendrites of nondopaminergic (primarily GABAergic) neurons in the substantia nigra, whereas the voltage-sensitive chloride channel 2 (ClC-2) was observed only in the dopaminergic neurons of the pars compacta. Electron-microscopic immunogold labeling confirmed that KCC2 is localized in the dendritic plasma membrane of GABAergic neurons close to inhibitory synapses. Confocal microscopy showed that ClC-2 was selectively expressed in the somatic and dendritic cell membranes of the dopaminergic neurons. Gramicidin-perforated-patch recordings revealed that the GABA(A) IPSP reversal potential was significantly less negative and had a much smaller hyperpolarizing driving force in dopaminergic than in GABAergic neurons. The GABA(A) reversal potential was significantly less negative in bicarbonate-free buffer in dopaminergic but not in GABAergic neurons. The present study suggests that KCC2 is responsible for maintaining the low intracellular Cl- concentration in nigral GABAergic neurons, whereas a sodium-dependent anion (Cl--HCO3-) exchanger and ClC-2 are likely to serve this role in dopaminergic neurons. The relatively low efficacy of GABAA-mediated inhibition in nigral dopaminergic neurons compared with nigral GABAergic neurons may be related to their lack of KCC2.
Indexed as
Identifiers
12967985PMC6740695W2137215947What 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.