| Functional contribution of the alpha7 subunit to multiple subtypes of nicotinic receptors in embryonic chick sympathetic neurones. | |
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MedLine Citation:
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PMID: 9596789 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. Many studies of the alpha7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) family have demonstrated that this alpha-bungarotoxin (alpha-BgTx)-binding neuronal receptor can participate in ACh-gated channels. Heterologous expression studies reveal that alpha7 subunits form homomeric channels of unusually high Ca2+ permeability. However, the physiological role of the alpha7 subunit in native neuronal nAChR channels is less clear. 2. We present evidence that the alpha7 subunit contributes to the function of at least three subtypes of native nAChR expressed by embryonic chick sympathetic neurones. These subtypes are functionally distinct from heterologously expressed homomeric alpha7 nAChRs as well as homomeric-like currents described in studies of hippocampal and parasympathetic neurones. 3. The proposed nAChRs differ from one another and from homomeric alpha7 nAChRs in their sensitivity to block by alpha7 subunit-specific antagonists: alpha-BgTx and methyllycaconitine (MLA). While MLA blocks 60 % of the macroscopic ACh response, alpha-BgTx inhibits a small component of the macroscopic current described by slow-on and slow-off kinetics. 4. Functional deletion of the alpha7 subunit by antisense oligonucleotide treatment eliminates the susceptibility of the nAChRs to block by both MLA and alpha-BgTx. 5. Single channel recordings combined with pharmacological and antisense-mediated 'deletion' techniques reveal that alpha-BgTx-sensitive alpha7-containing nAChRs have a small unitary conductance (18 pS), brief open time kinetics and relatively low open probability (Po). MLA-sensitive alpha7 nAChRs are characterized by a conductance of approximately 35 pS, intermediate burst duration, and a relatively high Po. 6. The third nAChR subtype deleted by alpha7 antisense treatment is characterized by a unitary conductance of 50 pS and prolonged opening duration. 7. We propose that these three populations of native alpha7-containing nAChRs are distinct heteromeric complexes that include other alpha and/or beta nAChR subunits. |
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Authors:
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C R Yu; L W Role |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of physiology Volume: 509 ( Pt 3) ISSN: 0022-3751 ISO Abbreviation: J. Physiol. (Lond.) Publication Date: 1998 Jun |
Date Detail:
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Created Date: 1998-08-06 Completed Date: 1998-08-06 Revised Date: 2010-06-04 |
Medline Journal Info:
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Nlm Unique ID: 0266262 Medline TA: J Physiol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 651-65 Citation Subset: IM |
Affiliation:
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Department of Anatomy and Cell Biology in the Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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pharmacology Aconitine / analogs & derivatives, pharmacology Animals Antisense Elements (Genetics) Bungarotoxins / pharmacology Calcium / pharmacology Chick Embryo Chlorides / pharmacokinetics Dose-Response Relationship, Drug Electric Conductivity Ganglia, Sympathetic / cytology* Gene Deletion Insecticides / pharmacology Ion Channel Gating / drug effects, physiology* Kinetics Mutagenesis / physiology Neurons / chemistry*, physiology Patch-Clamp Techniques Receptors, Nicotinic / chemistry, genetics* |
| Grant Support | |
ID/Acronym/Agency:
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NS 22061/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antisense Elements (Genetics); 0/Bungarotoxins; 0/Chlorides; 0/Insecticides; 0/Receptors, Nicotinic; 0/alpha7 nicotinic acetylcholine receptor; 21019-30-7/methyllycaconitine; 302-27-2/Aconitine; 51-84-3/Acetylcholine; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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