TY - JOUR
T1 - Ionic currents in normal and neurofibromatosis type 1-affected human schwann cells
T2 - Induction of tumor cell K current in normal schwann cells by cyclic AMP
AU - Fieber, L. A.
PY - 1998/11/15
Y1 - 1998/11/15
N2 - 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 non-inactivating 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 non-inactivating, 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.
AB - 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 non-inactivating 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 non-inactivating, 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.
KW - A current
KW - K current
KW - Na current
KW - Neurofibromatosis
KW - Patch clamp
KW - Proliferation
KW - Schwann cell
UR - http://www.scopus.com/inward/record.url?scp=0032533347&partnerID=8YFLogxK
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U2 - 10.1002/(SICI)1097-4547(19981115)54:4<495::AID-JNR7>3.0.CO;2-H
DO - 10.1002/(SICI)1097-4547(19981115)54:4<495::AID-JNR7>3.0.CO;2-H
M3 - Article
C2 - 9822160
AN - SCOPUS:0032533347
VL - 54
SP - 495
EP - 506
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 4
ER -