{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:42:38Z","timestamp":1792183358784,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2009,6,3]],"date-time":"2009-06-03T00:00:00Z","timestamp":1243987200000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:p>Inflammation has profound effects on the innervation of affected tissues, including altered neuronal excitability and neurotransmitter release. As Ca<jats:sup>2+<\/jats:sup> influx through voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> channels (VGCCs) is a critical determinant of excitation\u2013secretion coupling in nerve terminals, the aim of this study was to characterize the effect of overnight incubation in the inflammatory mediator tumour necrosis factor \u03b1 (TNF\u03b1; 1 n<jats:sc>m<\/jats:sc>) on VGCCs in dissociated neurons from mouse superior mesenteric ganglia (SMG). Voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> currents (<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>) were measured using the perforated patch clamp technique and the VGCC subtypes present in SMG neurons were estimated based on inhibition by selective VGCC blockers: \u03c9\u2010conotoxin GVIA (300 n<jats:sc>m<\/jats:sc>; N\u2010type), nifedipine (10 \u03bc<jats:sc>m<\/jats:sc>; L\u2010type), and \u03c9\u2010conotoxin MVIIC (300 n<jats:sc>m<\/jats:sc>; N\u2010, P\/Q\u2010type). We used intracellular Ca<jats:sup>2+<\/jats:sup> imaging with Fura\u20102 AM to compare Ca<jats:sup>2+<\/jats:sup> influx during depolarizations in control and TNF\u03b1\u2010treated neurons. TNF receptor and VGCC mRNA expression were measured using PCR, and channel \u03b1 subunit (CaV2.2) was localized with immunohistochemistry. Incubation in TNF\u03b1 significantly decreased <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> amplitude and depolarization\u2010induced Ca<jats:sup>2+<\/jats:sup> influx. The reduction in <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> was limited to \u03c9\u2010conotoxin GVIA\u2010sensitive N\u2010type Ca<jats:sup>2+<\/jats:sup> channels. Depletion of glial cells by incubation in cytosine arabinoside (5 \u03bc<jats:sc>m<\/jats:sc>) did not affect <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> inhibition by TNF\u03b1. Preincubation of neurons with SC\u2010514 (20 \u03bc<jats:sc>m<\/jats:sc>) or BAY 11\u20107082 (1 \u03bc<jats:sc>m<\/jats:sc>), which both inhibit nuclear factor \u03baB signalling, prevented the reduction in <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> by TNF\u03b1. Inhibition of N\u2010type VGCCs following TNF\u03b1 incubation was associated with a decrease in CaV2.2 mRNA and reduced membrane localization of CaV2.2 immunoreactivity. These data suggest that TNF\u03b1 inhibits <jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub> in SMG neurons and identify a novel role for NF\u2010\u03baB in the regulation of neurotransmitter release during inflammatory conditions with elevated circulating TNF\u03b1, such as Crohn's disease and Guillain\u2010Barr\u00e9 syndrome.<\/jats:p>","DOI":"10.1113\/jphysiol.2009.172312","type":"journal-article","created":{"date-parts":[[2009,4,30]],"date-time":"2009-04-30T00:34:06Z","timestamp":1241051646000},"page":"2623-2634","source":"Crossref","is-referenced-by-count":38,"title":["Tumour necrosis factor \u03b1 activates nuclear factor \u03baB signalling to reduce N\u2010type voltage\u2010gated Ca<sup>2+<\/sup> current in postganglionic sympathetic neurons"],"prefix":"10.1113","volume":"587","author":[{"given":"Mohamed A.","family":"Motagally","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark K.","family":"Lukewich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan P.","family":"Chisholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadia","family":"Neshat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan E.","family":"Lomax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,6,3]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01187084"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02064-5"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401259"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705249"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013322"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702256"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2003.08.001"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10169"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.09.005"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799890600915100"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.4.5"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000313647"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.01.070"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2297"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.03.005"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81057-0"},{"key":"e_1_2_5_18_1","first-page":"12","volume-title":"Textbook of Gastroenterology","author":"Furness JB","year":"2003"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90192-2"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70230-0"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2007.04.020"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1997.tb01637.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803336105"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200011303432202"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2006.02.015"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(95)00128-X"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705712"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00006.2009"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2083"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00521.2007"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3530-06.2006"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.3780050209"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.01.051"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/12153"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702629"},{"key":"e_1_2_5_36_1","first-page":"1390","article-title":"Enteric glia","volume":"53","author":"Sharkey KA","year":"2004","journal-title":"Gut"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021931"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(91)80011-W"},{"key":"e_1_2_5_39_1","first-page":"795","volume-title":"Physiology of the Gastrointestinal Tract","author":"Szurszewski JH","year":"1994"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702954"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.4.11"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.2006.3780120515.dd"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700948"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15676.x"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501229200"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.4035"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2009.172312","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2009.172312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T19:48:39Z","timestamp":1697312919000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2009.172312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6]]},"references-count":45,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2009,6]]}},"alternative-id":["10.1113\/jphysiol.2009.172312"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2009.172312","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6]]}}}