Enhanced Proliferation and Potassium Conductance of Schwann Cells Isolated from NF2 Schwannomas Can Be Reduced by Quinidine

C. Rosenbaum; M. Kamleiter; P. Grafe; L. Kluwe; V.-F. Mautner; H.W. Müller; C.O. Hanemann

Neurobiology of Disease (Aug 2000)

Enhanced Proliferation and Potassium Conductance of Schwann Cells Isolated from NF2 Schwannomas Can Be Reduced by Quinidine

C. Rosenbaum,
M. Kamleiter,
P. Grafe,
L. Kluwe,
V.-F. Mautner,
H.W. Müller,
C.O. Hanemann

Affiliations

C. Rosenbaum: Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine University, Duesseldorf, Germany; Department of Physiology, University of Munich, Munich, Germany; Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Department of Neurology, General Hospital North-Ochsenzoll, Hamburg, Germany; Department of Neurology, University Ulm, Ulm, Germany
M. Kamleiter: Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine University, Duesseldorf, Germany; Department of Physiology, University of Munich, Munich, Germany; Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Department of Neurology, General Hospital North-Ochsenzoll, Hamburg, Germany; Department of Neurology, University Ulm, Ulm, Germany
P. Grafe: Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine University, Duesseldorf, Germany; Department of Physiology, University of Munich, Munich, Germany; Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Department of Neurology, General Hospital North-Ochsenzoll, Hamburg, Germany; Department of Neurology, University Ulm, Ulm, Germany
L. Kluwe: Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine University, Duesseldorf, Germany; Department of Physiology, University of Munich, Munich, Germany; Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Department of Neurology, General Hospital North-Ochsenzoll, Hamburg, Germany; Department of Neurology, University Ulm, Ulm, Germany
V.-F. Mautner: Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine University, Duesseldorf, Germany; Department of Physiology, University of Munich, Munich, Germany; Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Department of Neurology, General Hospital North-Ochsenzoll, Hamburg, Germany; Department of Neurology, University Ulm, Ulm, Germany
H.W. Müller: Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine University, Duesseldorf, Germany; Department of Physiology, University of Munich, Munich, Germany; Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Department of Neurology, General Hospital North-Ochsenzoll, Hamburg, Germany; Department of Neurology, University Ulm, Ulm, Germany
C.O. Hanemann: Department of Neurology, Molecular Neurobiology Laboratory, Heinrich-Heine University, Duesseldorf, Germany; Department of Physiology, University of Munich, Munich, Germany; Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany; Department of Neurology, General Hospital North-Ochsenzoll, Hamburg, Germany; Department of Neurology, University Ulm, Ulm, Germany

Journal volume & issue: Vol. 7, no. 4
pp. 483 – 491

Abstract

Read online

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease that is characterized mainly by schwannomas, as well as menigiomas and gliomas. The NF2 gene product merlin/schwannomin acts as a tumor suppressor. Schwann cells derived from NF2 schwannomas showed an enhanced proliferation rate, and electrophysological studies revealed larger K+ outward currents as compared with controls. Schwann cells isolated from schwannomas of NF2 patients or multiorgan donors were treated with different concentrations of the K+ current blockers quinidine, tetraethylammonium chloride, and 4-aminopyridine and K+ outward currents and proliferation rates of these cells were compared. K+ outward currents of both cell types can be blocked by quinidine. Importantly, treatment with quinidine reduces proliferation of NF2 Schwann cells in a concentration dependent manner but did not reduce proliferation of normal Schwann cells. Therefore, the use of quinidine or quinidine-like components would possibly provide a novel adjuvant therapeutic option for NF2 patients to slow down or freeze growth of schwannomas.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

About the journal