Voltage-dependent membrane currents of cultured human neurofibromatosis type 2 Schwann cells.
Previous experimental observations indicate that inhibition of voltage-dependent K+ currents suppresses proliferation of normal Schwann cells. In the present study we tested the opposite relationship, i.e., whether Schwann cells from tumors with abnormally high rates of proliferation would have an increase in membrane K+ currents. Whole-cell membrane currents were studied in cultured cells from schwannomas of two neurofibromatosis type 2 (NF2) patients (n = 53), one patient with a sporadic schwannoma (n = 22), and two control subjects (n = 41). Five different types of voltage-dependent membrane currents were found in all of the Schwann cells tested. Membrane depolarization activated outward K+ and Cl- currents; quinidine was found to block the K+ current (IC50 approximately 1 microM), and NPPB reduced the Cl- current. Ba2+-sensitive inward rectifier K+ currents, fast Na+ currents, and a transient, inactivating K+ current were less frequently observed. On average, NF2 cells were found to have statistically significant higher membrane potential and larger non-inactivating K+ outward current as compared to controls. Electrophysiological parameters of Schwann cells from a sporadic schwannoma showed a tendency for larger outward currents; however, the difference did not reach statistical significance. Together the data support the suggestion of a possible link between K+ outward current and proliferation of Schwann cells.
Department of Physiology, University of Munich, Germany.
M
M
Kamleiter
C O
CO
Hanemann
L
L
Kluwe
C
C
Rosenbaum
S
S
Wosch
V F
VF
Mautner
H W
HW
Müller
P
P
Grafe
D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009442:Neurilemmoma / Q000473:pathology*; D016518:Neurofibromatosis 2 / Q000473:pathology*; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011802:Quinidine / Q000494:pharmacology; D012583:Schwann Cells / Q000473:pathology*; D015222:Sodium Channels / Q000502:physiology; D014407:Tumor Cells, Cultured
D018118:Chloride Channels; D009579:Nitrobenzoates; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D015222:Sodium Channels; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D011802:Quinidine