{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:07:44Z","timestamp":1783044464621,"version":"3.54.6"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,24]],"date-time":"2006-01-24T00:00:00Z","timestamp":1138060800000},"content-version":"vor","delay-in-days":876,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Lambert\u2010Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission in which antibodies are directed against voltage\u2010gated calcium channels (VGCCs). We studied the action of LEMS immunoglobulin G (IgG) on cloned human VGCCs stably transfected into human embryonic kidney cells (HEK293). All LEMS IgGs tested bound to the surface of the P\/Q\u2010type VGCC cell line and caused a significant reduction in whole\u2010cell calcium currents in these cells. By contrast, only 2 out of 6 IgGs bound extracellularly to the N\u2010type VGCC cell line, and none of the LEMS IgGs tested was able to reduce whole\u2010cell calcium currents in these cells. We used this apparent specificity of LEMS IgG for the P\/Q\u2010type VGCC to investigate the action of these IgGs on model systems where a number of different VGCC populations exist in equilibrium. LEMS IgG caused a significant downregulation in the \u03c9\u2010agatoxin IVA\u2010sensitive P\/Q\u2010type VGCCs of cultured rat cerebellar neurons, but this was accompanied by a concomitant rise in the \u201cresistant\u201d R\u2010type VGCCs. By using the passive transfer model of LEMS, similar results were observed at the mouse neuromuscular junction, where a significant reduction in P\/Q\u2010type VGCCs was paralleled by an increase in L\u2010 and R\u2010type VGCCs. These results demonstrate an unexpected plasticity in the expression of VGCCs in mammalian neurons and may represent a mechanism by which the pathogenic effects of LEMS IgG are reduced.<\/jats:p>","DOI":"10.1196\/annals.1254.019","type":"journal-article","created":{"date-parts":[[2004,1,15]],"date-time":"2004-01-15T01:04:15Z","timestamp":1074128655000},"page":"187-195","source":"Crossref","is-referenced-by-count":42,"title":["Pathogenic Autoantibodies in the Lambert\u2010Eaton Myasthenic Syndrome"],"prefix":"10.1111","volume":"998","author":[{"given":"BETHAN","family":"LANG","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ASHWIN","family":"PINTO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FEDERICA","family":"GIOVANNINI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JOHN","family":"NEWSOM\u2010DAVIS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANGELA","family":"VINCENT","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,24]]},"reference":[{"key":"e_1_2_8_2_2","first-page":"689","article-title":"Detailed analysis of neuromuscular transmission in a patient with the myasthenic syndrome sometimes associated with bronchogenic carcinoma","volume":"43","author":"Elmqvist D.","year":"1968","journal-title":"Mayo Clin. Proc."},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014943"},{"key":"e_1_2_8_4_2","first-page":"130","article-title":"Effect of Lambert\u2010Eaton syndrome immunoglobulins on autonomic neurons in the mouse","volume":"40","author":"Waterman S.A.","year":"1997","journal-title":"Ann. Neurol."},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/111.3.577"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00431-8"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(72)90179-9"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0198-8859(85)90062-X"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(01)00270-1"},{"key":"e_1_2_8_10_2","doi-asserted-by":"crossref","unstructured":"Wirtz P.W. N. Willcox B.O. Roepet al.2003. HLA\u2010B8 in patients with the Lambert\u2010Eaton myasthenic syndrome reduces likelihood of associated small cell lung carcinoma. This volume.","DOI":"10.1196\/annals.1254.021"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400510"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410250310"},{"key":"e_1_2_8_13_2","first-page":"200","article-title":"Lambert\u2010Eaton myasthenic syndrome: II","volume":"22","author":"Fukuoka T.","year":"1987","journal-title":"Immunoelectron microscopy localization of IgG at the mouse motor end-plate. Ann. Neurol."},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90021-3"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/355827a0"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(96)05303-8"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506013322203"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64041696.x"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.2.475"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8328"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10087"},{"key":"e_1_2_8_22_2","doi-asserted-by":"crossref","unstructured":"Giovannini F. E. Sher R. Websteret al.2002. Calcium channel subtypes contributing to acetylcholine release from normal 4\u2010aminopyridine\u2010treated and myasthenic syndrome auto\u2010antibodies\u2010affected neuromuscular junctions. Br. J. Pharmacol. In press.","DOI":"10.1038\/sj.bjp.0704818"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.5.1391"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.80.3.1056"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1254.019","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1254.019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T17:24:05Z","timestamp":1695662645000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1254.019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,9]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,9]]}},"alternative-id":["10.1196\/annals.1254.019"],"URL":"https:\/\/doi.org\/10.1196\/annals.1254.019","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,9]]}}}