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When calcium was administered directly into the cytoplasm, however, the IgG-treated cells exhibited normal exocytotic secretion, as assayed by membrane capacitance measurement. Measurement with the fluorescent calcium indicator fura-2 indicated that the IgG treatment reduced potassium-stimulated increase in free intracellular calcium concentration. The pathogenic IgG modified neither kinetics of calcium channel activation nor elementary channel activity, suggesting that a reduction in the number of functional calcium channels underlies the IgG-induced effect. Therefore, Lambert-Eaton syndrome IgG reacts with voltage-dependent calcium channels and blocks their function, a phenomenon that can account for the presynaptic impairment characteristic of this disorder.<\/jats:p>","DOI":"10.1126\/science.2447652","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T21:21:15Z","timestamp":1160083275000},"page":"405-408","source":"Crossref","is-referenced-by-count":148,"title":["IgG from Patients with Lambert-Eaton Syndrome Blocks Voltage-Dependent Calcium Channels"],"prefix":"10.1126","volume":"239","author":[{"given":"Yong I.","family":"Kim","sequence":"first","affiliation":[{"name":"Departments of Neurology and Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA 22908."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin","family":"Neher","sequence":"additional","affiliation":[{"name":"Departnent of Membrane Biophysics, Max-Planck-Institut f\u00fcr biophysikalische Chemie, Am Fassberg, D-3400 G6ttingen, F.R.G."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1146\/annurev.ne.10.030187.003221","volume":"10","year":"1987","unstructured":"AUGUSTINE, G.J., CALCIUM ACTION IN SYNAPTIC TRANSMITTER RELEASE, ANNUAL REVIEW OF NEUROSCIENCE 10: 633 (1987).","journal-title":"ANNUAL REVIEW OF NEUROSCIENCE"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1113\/jphysiol.1980.sp013145","volume":"299","year":"1980","unstructured":"CULLCANDY, S.G., RELEASE OF TRANSMITTER AT NORMAL, MYASTHENIA-GRAVIS AND MYASTHENIC SYNDROME AFFECTED HUMAN ENDPLATES, JOURNAL OF PHYSIOLOGY-LONDON 299: 621 (1980).","journal-title":"JOURNAL OF PHYSIOLOGY-LONDON"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1113\/jphysiol.1967.sp008367","volume":"193","year":"1967","unstructured":"DODGE, F.A., CO-OPERATIVE ACTION OF CALCIUM IONS IN TRANSMITTER RELEASE AT NEUROMUSCULAR JUNCTION, JOURNAL OF PHYSIOLOGY-LONDON 193: 419 (1967).","journal-title":"JOURNAL OF PHYSIOLOGY-LONDON"},{"key":"e_1_2_1_4_1","first-page":"689","volume":"43","year":"1968","unstructured":"ELMQVIST, D, DETAILED ANALYSIS OF NEUROMUSCULAR TRANSMISSION IN A PATIENT WITH MYASTHENIC SYNDROME SOMETIMES ASSOCIATED WITH BRONCHOGENIC CARCINOMA, MAYO CLINIC PROCEEDINGS 43: 689 (1968).","journal-title":"MAYO CLINIC PROCEEDINGS"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1113\/jphysiol.1982.sp014394","volume":"331","year":"1982","unstructured":"FENWICK, E.M., SODIUM AND CALCIUM CHANNELS IN BOVINE CHROMAFFIN CELLS, JOURNAL OF PHYSIOLOGY-LONDON 331: 599 (1982).","journal-title":"JOURNAL OF PHYSIOLOGY-LONDON"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/mus.880050905","volume":"5","year":"1982","unstructured":"FUKUNAGA, H, PAUCITY AND DISORGANIZATION OF PRE-SYNAPTIC MEMBRANE ACTIVE ZONES IN THE LAMBERT-EATON MYASTHENIC SYNDROME, MUSCLE & NERVE 5: 686 (1982).","journal-title":"MUSCLE & NERVE"},{"key":"e_1_2_1_7_1","first-page":"7636","volume":"80","year":"1983","unstructured":"FUKUNAGA, H, PASSIVE TRANSFER OF LAMBERT-EATON MYASTHENIC SYNDROME WITH IGG FROM MAN TO MOUSE DEPLETES THE PRESYNAPTIC MEMBRANE ACTIVE ZONES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 80: 7636 (1983).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/ana.410220203","volume":"22","year":"1987","unstructured":"FUKUOKA, T, LAMBERT-EATON MYASTHENIC SYNDROME .1. 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