title: Ionic currents in normal and neurofibromatosis type 1-affected human Schwann cells: induction of tumor cell K current in normal Schwann cells by cyclic AMP.
abstract: Comparisons were made of whole cell voltage clamp recordings from cultures of normal Schwann cells (SC) from three human subjects and from three neurofibrosarcoma cell lines. The whole cell K+ (K) currents of normal and tumor cells could be divided into three types based on voltage activation range, pharmacology, and macroscopic inactivation: A type current, tetraethylammonium- (TEA-) only-sensitive current, and inward rectifier current. The most conspicuous difference between normal and tumor cells was the nature of K currents present. Normal SC K currents were inactivating, A type currents blocked by extracellular 4-aminopyridine (4-AP; 5 mM). The whole cell K currents of tumor cells were noninactivating due to the presence of non-inactivating A current, or non-inactivating, TEA-only sensitive current, or both, despite the presence of inactivating A current in some tumor cells. TEA-only-sensitive currents, which were 4-AP-insensitive and noninactivating, were common in all three tumor cell lines, but were not observed in normal SC. Inward rectifier K currents were a conspicuous feature of two of the tumor cells lines but were rarely observed in whole cell recordings of normal SC. The properties of Na+ currents recorded in both normal and tumor cells were not significantly different. Treatment of normal SC with a membrane-permeant analog of cyclic AMP (cAMP) resulted in functional expression of the TEA-only-sensitive K currents typical of tumor cells. These results establish the abnormal ion channel profile of neurofibromatosis type 1 (NF1)-tumor cells and suggest (Guo et al.: Science 276:795-798, 1997) that regulation of ionic currents by second messengers may involve the NF1 gene.
authors.affiliation: University of Miami Rosenstiel School of Marine and Atmospheric Science, Florida, USA. lfieber@rsmas.miami.edu
authors.forename: L A
authors.initials: LA
authors.lastname: Fieber
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000293:Adolescent; D003994:Bucladesine / Q000494:pharmacology; D002420:Cauda Equina; D002478:Cells, Cultured; D002648:Child; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009456:Neurofibromatosis 1 / Q000378:metabolism* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D007473:Ion Channels; D015221:Potassium Channels; D013873:Thionucleotides; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D013779:Tetrodotoxin; D003994:Bucladesine; D019789:Tetraethylammonium; D012964:Sodium; D015761:4-Aminopyridine; D000242:Cyclic AMP; D011188:Potassium