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

Comparisons were made of whole cell voltage clamp recordings from cult ures of normal Schwann cells (SC) from three human subjects and from t hree neurofibrosarcoma cell lines. The whole cell K+ (K) currents of n ormal and tumor cells could be divided into three types based on volta ge activation range, pharmacology, and macroscopic inactivation: A typ e current, tetraethylammonium- (TEA-) only-sensitive current, and inwa rd rectifier current. The most conspicuous difference between normal a nd tumor cells was the nature of K currents present, Normal SC K curre nts were inactivating, A type currents blocked by extracellular 4-amin opyridine (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 pre sence of inactivating A current in some tumor cells, TEA-only-sensitiv e currents, which were 4-AP-insensitive and noninactivating, were comm on 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 t umor 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 w ith a membrane-permeant analog of cyclic AMP (cAMP) resulted in functi onal expression of the TEA-only-sensitive K currents typical of tumor cells, These results establish the abnormal ion channel profile of neu rofibromatosis type 1 (NF1)-tumor cells and suggest (Guo et al,: Scien ce 276:795-798, 1997) that regulation of ionic currents by second mess engers may involve the NF1 gene. J. Neurosci. Res, 54:495-506, 1998, ( C) 1998 Wiley-Liss, Inc.