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dc.contributor.authorLiu, Liwang
dc.contributor.authorRittenhouse, Ann R.
dc.date2022-08-11T08:09:36.000
dc.date.accessioned2022-08-23T16:37:08Z
dc.date.available2022-08-23T16:37:08Z
dc.date.issued2002-12-24
dc.date.submitted2009-04-02
dc.identifier.citation<p>Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):295-300. Epub 2002 Dec 20. <a href="http://dx.doi.org/10.1073/pnas.0136826100">Link to article on publisher's site</a></p>
dc.identifier.issn0027-8424 (Print)
dc.identifier.doi10.1073/pnas.0136826100
dc.identifier.pmid12496347
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38944
dc.description.abstractN-type Ca(2+) channels participate in acute activity-dependent processes such as regulation of Ca(2+)-activated K(+) channels and in more prolonged events such as gene transcription and long-term depression. A slow postsynaptic M(1) muscarinic receptor-mediated modulation of N-type current in superior cervical ganglion neurons may be important in regulating these processes. This slow pathway inhibits N-type current by using a diffusible second messenger that has remained unidentified for more than a decade. Using whole-cell patch-clamp techniques, which isolate the slow pathway, we found that the muscarinic agonist oxotremorine methiodide not only inhibits currents at positive potentials but enhances N-type current at negative potentials. Enhancement was also observed in cell-attached patches. These findings provide evidence for N-type Ca(2+)-current enhancement by a classical neurotransmitter. Moreover, enhancement and inhibition of current by oxotremorine methiodide mimics modulation observed with direct application of a low concentration of arachidonic acid (AA). Although no transmitter has been reported to use AA as a second messenger to modulate any Ca(2+) current in either neuronal or nonneuronal cells, we nevertheless tested whether a fatty acid signaling cascade was involved. Blocking phospholipase C, phospholipase A(2), or AA but not AA metabolism minimized muscarinic modulation of N-type current, supporting the participation of these molecules in the slow pathway. A role for the G protein G(q) was also confirmed by blocking muscarinic modulation of Ca(2+) currents with anti-G(qalpha) antibody. Our finding that AA participates in the slow pathway strongly suggests that it may be the previously unknown diffusible second messenger.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=12496347&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC140955/
dc.subjectAnimals
dc.subjectAnimals, Newborn
dc.subjectArachidonic Acid
dc.subjectCalcium Channel Blockers
dc.subjectCalcium Channels, N-Type
dc.subjectMembrane Potentials
dc.subjectMuscarinic Antagonists
dc.subjectNeurons
dc.subjectNimodipine
dc.subjectOxotremorine
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReceptor, Muscarinic M1
dc.subjectReceptors, Muscarinic
dc.subjectSuperior Cervical Ganglion
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleArachidonic acid mediates muscarinic inhibition and enhancement of N-type Ca2+ current in sympathetic neurons
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume100
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1774
dc.identifier.contextkey808539
html.description.abstract<p>N-type Ca(2+) channels participate in acute activity-dependent processes such as regulation of Ca(2+)-activated K(+) channels and in more prolonged events such as gene transcription and long-term depression. A slow postsynaptic M(1) muscarinic receptor-mediated modulation of N-type current in superior cervical ganglion neurons may be important in regulating these processes. This slow pathway inhibits N-type current by using a diffusible second messenger that has remained unidentified for more than a decade. Using whole-cell patch-clamp techniques, which isolate the slow pathway, we found that the muscarinic agonist oxotremorine methiodide not only inhibits currents at positive potentials but enhances N-type current at negative potentials. Enhancement was also observed in cell-attached patches. These findings provide evidence for N-type Ca(2+)-current enhancement by a classical neurotransmitter. Moreover, enhancement and inhibition of current by oxotremorine methiodide mimics modulation observed with direct application of a low concentration of arachidonic acid (AA). Although no transmitter has been reported to use AA as a second messenger to modulate any Ca(2+) current in either neuronal or nonneuronal cells, we nevertheless tested whether a fatty acid signaling cascade was involved. Blocking phospholipase C, phospholipase A(2), or AA but not AA metabolism minimized muscarinic modulation of N-type current, supporting the participation of these molecules in the slow pathway. A role for the G protein G(q) was also confirmed by blocking muscarinic modulation of Ca(2+) currents with anti-G(qalpha) antibody. Our finding that AA participates in the slow pathway strongly suggests that it may be the previously unknown diffusible second messenger.</p>
dc.identifier.submissionpathoapubs/1774
dc.contributor.departmentDepartment of Physiology
dc.contributor.departmentProgram in Neuroscience
dc.source.pages295-300


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