{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:07:51Z","timestamp":1783044471171,"version":"3.54.6"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,9,1]],"date-time":"2002-09-01T00:00:00Z","timestamp":1030838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2002,9]]},"abstract":"<jats:p>Lambert\u2010Eaton myasthenic syndrome (LEMS) is a paraneoplastic disorder in which autoantibodies apparently target the voltage\u2010gated Ca<jats:sup>2+<\/jats:sup> channels that regulate acetylcholine (ACh) release at motor nerve terminals. P\/Q\u2010type Ca<jats:sup>2+<\/jats:sup> channels are primarily involved in ACh release at mammalian neuromuscular junctions. Passive transfer of LEMS to mice by repeated administration of plasma from LEMS patients reduces the amplitude of the perineurial P\/Q\u2010type current, and unmasks a dihydropyridine (DHP)\u2010sensitive L\u2010type Ca<jats:sup>2+<\/jats:sup> current at the motor nerve terminal. The present study sought to determine if this DHP\u2010sensitive component contributes to ACh release. Mice were treated for 30 days with plasma from healthy human controls or patients with LEMS. For some studies, diaphragms from naive mice were incubated with LEMS or control human plasma for 2 or 24 h. End\u2010plate potentials (EPPs) and miniature end\u2010plate potentials (MEPPs) were recorded from neuromuscular junctions in the hemidiaphragm. Treatment of mice with LEMS plasma evoked the characteristic electrophysiological signs of LEMS: reduced quantal content and facilitation of EPP amplitudes at high\u2010frequency stimulation. Quantal content was also reduced in muscles incubated acutely with LEMS plasma. Nimodipine, a DHP\u2010type blocker of L\u2010type Ca<jats:sup>2+<\/jats:sup> channels, did not significantly affect the quantal content of muscles treated for 2 or 24 h with either control or LEMS plasma, or following chronic treatment with control plasma. However, following 30 days treatment with LEMS plasma, nimodipine significantly reduced the remaining quantal content to 57.7 \u00b1 3.3% of pre\u2010nimodipine control levels. Thus, DHP\u2010sensitive Ca<jats:sup>2+<\/jats:sup> channels become involved in synaptic transmission at the mouse neuromuscular junction after chronic, but not acute treatment with LEMS plasma. However, reductions in quantal release of ACh occur even after very short periods of exposure to LEMS plasma. As such, development of the L\u2010type Ca<jats:sup>2+<\/jats:sup> channel contribution to ACh release during passive transfer of LEMS appears to occur only after quantal release is significantly impaired for an extended duration, suggesting that an adaptive response of the ACh release apparatus occurs in LEMS.<\/jats:p>","DOI":"10.1113\/jphysiol.2002.021048","type":"journal-article","created":{"date-parts":[[2002,8,30]],"date-time":"2002-08-30T21:23:00Z","timestamp":1030742580000},"page":"567-576","source":"Crossref","is-referenced-by-count":30,"title":["Passive transfer of Lambert\u2010Eaton syndrome to mice induces dihydropyridine sensitivity of neuromuscular transmission"],"prefix":"10.1113","volume":"543","author":[{"given":"Michael T.","family":"Flink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Atchison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,9]]},"reference":[{"key":"e_1_2_5_1_1","first-page":"672","article-title":"Dihydropyridine\u2010sensitive and \u2010insensitive components of acetylcholine release from rat motor nerve terminals","volume":"251","author":"Atchison W. 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