Voltage‐Gated ion currents of schwann cells in cell culture models of human neurofibromatosis

Abstract

K(+) (K) channels play a role in the proliferation of many cell types in normal cells and certain disease states. Several laboratories have studied K currents in cultured Schwann cells from models of the human diseases, neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). These diseases are characterized by the growth of Schwann cell tumors. In all cell culture NF models the K current properties differ in tumor-derived and normal Schwann cells. Depending on the model however, the type of K channel abnormality differs. K channels appear to play a role in the proliferation of Schwann cell cultures of these disease models, because a link has been established between K current blockade and the inhibition of Schwann cell proliferation in NF1 and NF2. Differences in the proliferation response of normal Schwann cells to K channel blockers suggest that in vitro regulation of proliferation in neoplastic and normal Schwann cells is complex.

Local Anesthetic Schwann Cell Toxicity Is Time and Concentration Dependent

“…Expression of ion channels involved in regulation of cell proliferation is abnormal in neoplastic Schwann cells. 38 Schwann cells from tumor cell lines display abnormal cell-surface ligands implicated in cell migration, cell-matrix interaction, and tumor progression such as CD44. 39 Because we have used cells harvested directly from rat peripheral nerves, our study may more accurately reflect the effects of LAs on normal nerves in vivo.…”

Altered calcium currents and axonal growth in Nf1 haploinsufficient mice

“…Although whole cell voltage clamp analysis on neurofibromin deficient Schwann cells has demonstrated alterations in potassium currents [10–12], to date there have been no studies addressing if ion channel activity is altered in neurons from Nf1 +/− mice. Our study addressed this gap in knowledge by measuring calcium currents from hippocampal neurons of wild-type and Nf1 +/− mice.…”

“…However, to date there have been no studies addressing if calcium channel activity is altered in neurons from neurofibromin deficient mice. Using whole cell voltage clamp analysis, it was shown that potassium currents are altered in neurofibromin deficient Schwann cells [10–12], and a recent study demonstrated augmented sodium currents in sensory neurons from Nf1 +/− mice [13]. Here, we examined the complement of calcium channels underlying transmitter release in hippocampal neurons from wildtype and Nf1 +/− mice.…”