Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice
In the sympathetic superior cervical ganglion (SCG), nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission. We previously demonstrated that in SCG neurons of mdx mice, an animal model for Duchenne muscular dystrophy, lack of dystrophin causes a decrease, compared to the wild-...
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| Format: | Article |
| Language: | English |
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Elsevier
2011-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996110003670 |
| _version_ | 1818742184702115840 |
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| author | Silvia Di Angelantonio Maria Egle De Stefano Alessio Piccioni Loredana Lombardi Cecilia Gotti Paola Paggi |
| author_facet | Silvia Di Angelantonio Maria Egle De Stefano Alessio Piccioni Loredana Lombardi Cecilia Gotti Paola Paggi |
| author_sort | Silvia Di Angelantonio |
| collection | DOAJ |
| description | In the sympathetic superior cervical ganglion (SCG), nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission. We previously demonstrated that in SCG neurons of mdx mice, an animal model for Duchenne muscular dystrophy, lack of dystrophin causes a decrease, compared to the wild-type, in post-synaptic nAChRs containing the α3 subunit associated with β2 and/or β4 (α3β2/β4-nAChRs), but not in those containing the α7 subunit. Here we show, by whole cell patch-clamp recordings from cultured SCG neurons, that both nicotine and acetylcholine-evoked currents through α3β2/β4-nAChRs are significantly reduced in mdx mice compared to the wild-type, while those through α7-nAChR are unaffected. This reduction associates with that of protein levels of α3, β2 and β4 subunits. Therefore, we suggest that, in mdx mouse SCG neurons, lack of dystrophin, by specifically affecting membrane stabilization of α3β2/β4-nAChRs, could determine an increase in receptor internalization and degradation, with consequent reduction in the fast intraganglionic cholinergic transmission. |
| first_indexed | 2024-12-18T02:08:29Z |
| format | Article |
| id | doaj.art-b27555cfbaee4dfba8742c753a192a51 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-18T02:08:29Z |
| publishDate | 2011-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-b27555cfbaee4dfba8742c753a192a512022-12-21T21:24:33ZengElsevierNeurobiology of Disease1095-953X2011-02-01412528537Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx miceSilvia Di Angelantonio0Maria Egle De Stefano1Alessio Piccioni2Loredana Lombardi3Cecilia Gotti4Paola Paggi5Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie “Charles Darwin,” Sapienza Università di Roma, Italy; Center for Research in Neurobiology “Daniel Bovet”, Sapienza Università di Roma, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie “Charles Darwin,” Sapienza Università di Roma, Italy; Center for Research in Neurobiology “Daniel Bovet”, Sapienza Università di Roma, Italy; Corresponding author. Dip. Biologia e Biotecnologie “Charles Darwin”, Sapienza Università di Roma, P.le A. Moro 5-00185 Roma, Italy. Fax: +39 06 4991 2351.Dipartimento di Fisiologia e Farmacologia Sapienza Università di Roma, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie “Charles Darwin,” Sapienza Università di Roma, ItalyCNR, Istituto di Neuroscienze, Farmacologia Cellulare e Molecolare e Dipartimento Farmacologia, Chemioterapia e Tossicologia Medica, Università degli Studi di Milano, ItalyIstituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie “Charles Darwin,” Sapienza Università di Roma, Italy; Center for Research in Neurobiology “Daniel Bovet”, Sapienza Università di Roma, ItalyIn the sympathetic superior cervical ganglion (SCG), nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission. We previously demonstrated that in SCG neurons of mdx mice, an animal model for Duchenne muscular dystrophy, lack of dystrophin causes a decrease, compared to the wild-type, in post-synaptic nAChRs containing the α3 subunit associated with β2 and/or β4 (α3β2/β4-nAChRs), but not in those containing the α7 subunit. Here we show, by whole cell patch-clamp recordings from cultured SCG neurons, that both nicotine and acetylcholine-evoked currents through α3β2/β4-nAChRs are significantly reduced in mdx mice compared to the wild-type, while those through α7-nAChR are unaffected. This reduction associates with that of protein levels of α3, β2 and β4 subunits. Therefore, we suggest that, in mdx mouse SCG neurons, lack of dystrophin, by specifically affecting membrane stabilization of α3β2/β4-nAChRs, could determine an increase in receptor internalization and degradation, with consequent reduction in the fast intraganglionic cholinergic transmission.http://www.sciencedirect.com/science/article/pii/S0969996110003670Nicotinic acetylcholine receptorsDuchenne muscular dystrophyAutonomic neuronsWestern immunoblotImmunohistochemistryPatch-clamp recording |
| spellingShingle | Silvia Di Angelantonio Maria Egle De Stefano Alessio Piccioni Loredana Lombardi Cecilia Gotti Paola Paggi Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice Neurobiology of Disease Nicotinic acetylcholine receptors Duchenne muscular dystrophy Autonomic neurons Western immunoblot Immunohistochemistry Patch-clamp recording |
| title | Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice |
| title_full | Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice |
| title_fullStr | Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice |
| title_full_unstemmed | Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice |
| title_short | Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice |
| title_sort | lack of dystrophin functionally affects α3β2 β4 nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice |
| topic | Nicotinic acetylcholine receptors Duchenne muscular dystrophy Autonomic neurons Western immunoblot Immunohistochemistry Patch-clamp recording |
| url | http://www.sciencedirect.com/science/article/pii/S0969996110003670 |
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