| Diabetes depresses synaptic transmission in sympathetic ganglia by inactivating nAChRs through a conserved intracellular cysteine residue. | |
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MedLine Citation:
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PMID: 20620869 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Most people with diabetes develop severe complications of the autonomic nervous system; yet, the underlying causes of many diabetic-induced dysautonomias are poorly understood. Here we explore the idea that these dysautonomias results, in part, from a defect in synaptic transmission. To test this idea, we investigated cultured sympathetic neurons and show that hyperglycemia inactivates nAChRs through a mechanism involving an elevation in reactive oxygen species and an interaction with highly conserved cysteine residues located near the intracellular mouth of the nAChR channel. Consistent with this, we show that diabetic mice have depressed ganglionic transmission and reduced sympathetic reflexes, whereas diabetic mice expressing mutant postsynaptic nAChRs that lack the conserved cysteine residues on the alpha3 subunit have normal synaptic transmission in sympathetic ganglia and normal sympathetic reflexes. Our work suggests a new model for diabetic-induced dysautonomias and identifies ganglionic nAChRs as targets of hyperglycemia-induced downstream signals. |
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Authors:
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Verónica Campanucci; Arjun Krishnaswamy; Ellis Cooper |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neuron Volume: 66 ISSN: 1097-4199 ISO Abbreviation: Neuron Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-07-12 Completed Date: 2010-08-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8809320 Medline TA: Neuron Country: United States |
Other Details:
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Languages: eng Pagination: 827-34 Citation Subset: IM |
Affiliation:
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Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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pharmacology Adenoviridae Age Factors Aldehydes / metabolism Animals Animals, Newborn Body Temperature / drug effects, physiology Cells, Cultured Cysteine / genetics, metabolism* Diabetes Mellitus, Experimental / chemically induced, pathology* Disease Models, Animal Enzyme Inhibitors / pharmacology Excitatory Postsynaptic Potentials / drug effects, genetics Glucose / pharmacology Guanidines / pharmacology Heart Rate / drug effects, physiology Hypoglycemic Agents / pharmacology Insulin / pharmacology Leptin / genetics Mice Mice, Inbred C57BL Mice, Transgenic Mutation / genetics Oxidative Stress / drug effects, physiology Patch-Clamp Techniques Reactive Oxygen Species / metabolism Receptors, Leptin / genetics Receptors, Nicotinic / deficiency, metabolism* Sensory Receptor Cells / physiology* Superior Cervical Ganglion / pathology* Synaptic Transmission / drug effects, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Aldehydes; 0/Enzyme Inhibitors; 0/Guanidines; 0/Hypoglycemic Agents; 0/Leptin; 0/Reactive Oxygen Species; 0/Receptors, Leptin; 0/Receptors, Nicotinic; 0/nicotinic receptor subunit alpha3; 11061-68-0/Insulin; 29343-52-0/4-hydroxy-2-nonenal; 50-99-7/Glucose; 51-84-3/Acetylcholine; 52-90-4/Cysteine; 79-17-4/pimagedine |
| Comments/Corrections | |
Comment In:
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Neuron. 2010 Jun 24;66(6):809-11
[PMID:
20620864
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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