Enhanced proliferation and potassium conductance of schwann cells isolatedfrom NF2 schwannomas can be reduced by quinidine

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease that is cha racterized mainly by schwannomas, as well as menigiomas and gliomas. The NF 2 gene product merlin/schwannomin acts as a tumor suppressor. Schwann cells derived from NF2 schwannomas showed an enhanced proliferation rate, and el ectrophysological studies revealed larger K+ outward currents as compared w ith controls. Schwann cells isolated from schwannomas of NF2 patients or mu ltiorgan donors were treated with different concentrations of the K+ curren t 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. Importan tly, treatment with quinidine reduces proliferation of NF2 Schwann cells in a concentration dependent manner but did not reduce proliferation of norma l Schwann cells. Therefore, the use of quinidine or quinidine-like componen ts would possibly provide a novel adjuvant therapeutic option for NF2 patie nts to slow down or freeze growth of schwannomas. (C) 2000 Academic Press.