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Lambert-Eaton myasthenic syndrome immunoglobulins react with multiple types of calcium channels in small-cell lung carcinoma.

Abstract
Barium currents through voltage-gated calcium (Ca2+) channels were studied in the small-cell lung carcinoma cell line NCI-H345 using patch clamp techniques. Pharmacological dissection of whole-cell barium currents revealed that 23% of the current was sensitive to nitrendipine, 35% to omega-conotoxin GVIA, and between 10 and 39% to omega-Aga-IVA. This implies that these cells express L-, N-, and P-type calcium channels. Only large cells expressed current that was sensitive to omega-Aga-IVA. The size dependency of this P-type channel expression may reflect the cell cycle stage. Cell-attached recordings revealed three unitary conductances: 5 to 6 pS, 10 to 12 pS, and 20 to 23 pS. The largest conductance channel (20-23 pS) was sensitive to Bay K 8644 and is presumed to represent L-type calcium channels. The frequency of observing the medium conductance channel (10-12 pS) was reduced by exposure to omega-conotoxin GVIA and may represent N-type channels. Incubation of cells with Lambert-Eaton myasthenic syndrome IgG for 24 to 48 hours removed up to 71% of the whole-cell current. Incubation with control human IgG (normal or myasthenia gravis) had no effect. Lambert-Eaton myasthenic syndrome IgG did not selectively target one "presynaptic" type of calcium channel, but rather appeared to target many of the calcium channel types that are expressed on small-cell lung carcinoma cells.
AuthorsS D Meriney, S C Hulsizer, V A Lennon, A D Grinnell
JournalAnnals of neurology (Ann Neurol) Vol. 40 Issue 5 Pg. 739-49 (Nov 1996) ISSN: 0364-5134 [Print] United States
PMID8957015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Autoantibodies
  • Calcium Channel Blockers
  • Calcium Channels
  • Peptides
  • Spider Venoms
  • omega-Agatoxin IVA
  • Barium
  • omega-Conotoxin GVIA
  • Nitrendipine
Topics
  • Autoantibodies (blood)
  • Barium (pharmacology)
  • Calcium Channel Blockers (pharmacology)
  • Calcium Channels (immunology, physiology)
  • Carcinoma, Small Cell
  • Cell Cycle
  • Cell Line
  • Cell Membrane (drug effects, physiology)
  • Humans
  • Lambert-Eaton Myasthenic Syndrome (immunology)
  • Lung Neoplasms
  • Membrane Potentials (drug effects)
  • Nitrendipine (pharmacology)
  • Patch-Clamp Techniques
  • Peptides (pharmacology)
  • Spider Venoms (pharmacology)
  • omega-Agatoxin IVA
  • omega-Conotoxin GVIA

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