title: Enhanced proliferation and potassium conductance of Schwann cells isolated from NF2 schwannomas can be reduced by quinidine.
abstract: 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.
authors.affiliation: Department of Neurology, Heinrich-Heine University, Duesseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rosenbaum
authors.forename: M
authors.initials: M
authors.lastname: Kamleiter
authors.forename: P
authors.initials: P
authors.lastname: Grafe
authors.forename: L
authors.initials: L
authors.lastname: Kluwe
authors.forename: V
authors.initials: V
authors.lastname: Mautner
authors.forename: H W
authors.initials: HW
authors.lastname: Müller
authors.forename: C O
authors.initials: CO
authors.lastname: Hanemann
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009442:Neurilemmoma / Q000188:drug therapy / Q000503:physiopathology; D016518:Neurofibromatosis 2 / Q000188:drug therapy / Q000503:physiopathology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011802:Quinidine / Q000494:pharmacology* / Q000627:therapeutic use; D012583:Schwann Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011802:Quinidine