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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)495-506
Number of pages12
JournalJournal of Neuroscience Research
Volume54
Issue number4
DOIs
StatePublished - Nov 15 1998

Fingerprint

Neurofibromatosis 1
Schwann Cells
Cyclic AMP
Tetraethylammonium
Neoplasms
Tumor Cell Line
Neurofibrosarcoma
Neurofibromatosis 1 Genes
4-Aminopyridine
Second Messenger Systems
Patch-Clamp Techniques
Ion Channels
Pharmacology
Cell Line

Keywords

  • A current
  • K current
  • Na current
  • Neurofibromatosis
  • Patch clamp
  • Proliferation
  • Schwann cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{5d0addbc25fb40b5abf42be3ce51daf6,
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 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.",
keywords = "A current, K current, Na current, Neurofibromatosis, Patch clamp, Proliferation, Schwann cell",
author = "Fieber, {Lynne A}",
year = "1998",
month = "11",
day = "15",
doi = "10.1002/(SICI)1097-4547(19981115)54:4<495::AID-JNR7>3.0.CO;2-H",
language = "English",
volume = "54",
pages = "495--506",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "4",

}

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, Lynne 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

UR - http://www.scopus.com/inward/citedby.url?scp=0032533347&partnerID=8YFLogxK

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 -