{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:07:46Z","timestamp":1783044466315,"version":"3.54.6"},"reference-count":61,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1998,9,1]]},"abstract":"<jats:p>Xu, You-Fen, Sandra J. Hewett, and William D. Atchison. Passive transfer of Lambert-Eaton Myasthenic Syndrome induces dihydropyridine sensitivity of I<jats:sub>Ca<\/jats:sub>in mouse motor nerve terminals. J. Neurophysiol. 80: 1056\u20131069, 1998. Mice were injected for 30 days with plasma from three patients with Lambert-Eaton Myasthenic Syndrome (LEMS). Recordings were made from the perineurial sheath of motor axon terminals of triangularis sterni muscle preparations. The objective was to characterize pharmacologically the identity of kinetically distinct, defined potential changes associated with motor nerve terminal Ca<jats:sup>2+<\/jats:sup>currents ( I<jats:sub>Ca<\/jats:sub>) that were affected by LEMS autoantibodies. I<jats:sub>Ca<\/jats:sub>elicited at 0.01 Hz were significantly reduced in amplitude by \u223c35% of control in LEMS-treated nerve terminals. During 10-Hz stimulation, I<jats:sub>Ca<\/jats:sub>amplitude was unchanged in LEMS-treated motor nerve terminals, but was depressed in control. During 20- or 100-Hz trains, facilitation of I<jats:sub>Ca<\/jats:sub>occurred in LEMS-treated nerve terminals whereas in control, no facilitation occurred during the trains at 20 Hz and marked depression occurred at 100 Hz. Saturation for amplitude and duration of I<jats:sub>Ca<\/jats:sub>in control terminals occurred at 2 and 4\u20136 mM extracellular Ca<jats:sup>2+<\/jats:sup>, respectively; in LEMS-treated terminals, the extracellular Ca<jats:sup>2+<\/jats:sup>concentration had to increase by two to three times of control to cause saturation. Amplitude of the two components of I<jats:sub>Ca<\/jats:sub>observed when the preparation was exposed to 50 \u03bcM 3,4-diaminopyridine and 1 mM tetraethylammonium were both reduced by LEMS plasma treatment. The fast component ( I<jats:sub>Ca,f<\/jats:sub>) was reduced by 35%, whereas the slow component ( I<jats:sub>Ca,s<\/jats:sub>) was reduced by 37%. \u03c9-Agatoxin IVA (\u03c9-Aga-IVA; 0.15 \u03bcM) and \u03c9-conotoxin-MVIIC (\u03c9-CTx-MVIIC; 5 \u03bcM) completely blocked I<jats:sub>Ca<\/jats:sub>in control motor nerve terminals. The same concentrations of toxins were 20\u201330% less effective in blocking I<jats:sub>Ca<\/jats:sub>in LEMS-treated terminals. The residual I<jats:sub>Ca<\/jats:sub>remaining after treatment with \u03c9-Aga-IVA or \u03c9-CTx-MVIIC was blocked by 10 \u03bcM nifedipine and 10 \u03bcM Cd<jats:sup>2+<\/jats:sup>. Thus LEMS plasma appears to downregulate \u03c9-Aga-IVA-sensitive (P-type) and\/or \u03c9-CTx-MVIIC-sensitive (Q- type) Ca<jats:sup>2+<\/jats:sup>channels in murine motor nerve terminals, whereas dihydropyridine (DHP)-sensitive (L-type) Ca<jats:sup>2+<\/jats:sup>channels are unmasked in these terminals. Acute exposure (90 min) of rat forebrain synaptosomes to LEMS immunoglobulins (Igs; 4 mg\/ml) did not alter the binding of [<jats:sup>3<\/jats:sup>H]-nitrendipine or [<jats:sup>125<\/jats:sup>I]-\u03c9-conotoxin-GVIA (-\u03c9-CgTx GVIA) when compared with synaptosomes incubated with an equivalent concentration of control Igs. Conversely, LEMS Igs significantly decreased the B<jats:sub>max<\/jats:sub>for [<jats:sup>3<\/jats:sup>H]-verapamil to \u223c45% of control. The apparent affinity of verapamil ( K<jats:sub>D<\/jats:sub>) for the remaining receptors was not significantly altered. Thus acute exposure of isolated central nerve terminals to LEMS Igs does not increase DHP sensitivity, whereas it reduces the number of binding sites for verapamil but not for nitrendipine or \u03c9-CgTx-GVIA. These results suggest that chronic but not acute exposure to LEMS Igs either upregulates or unmasks DHP-sensitive Ca<jats:sup>2+<\/jats:sup>channels in motor nerve endings.<\/jats:p>","DOI":"10.1152\/jn.1998.80.3.1056","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T04:51:09Z","timestamp":1514177469000},"page":"1056-1069","source":"Crossref","is-referenced-by-count":27,"title":["Passive Transfer of Lambert-Eaton Myasthenic Syndrome Induces Dihydropyridine Sensitivity of<i>I<\/i><sub>Ca<\/sub>in Mouse Motor Nerve Terminals"],"prefix":"10.1152","volume":"80","author":[{"given":"You-Fen","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Neuroscience Program and Institute of Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824-1317"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra J.","family":"Hewett","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Neuroscience Program and Institute of Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824-1317"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Atchison","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Neuroscience Program and Institute of Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824-1317"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(87)90125-X"},{"key":"B2","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/S0022-3565(25)20860-6","volume":"251","author":"Atchison W. 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