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K + channel block‐induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation
Author(s) -
RouzaireDubois B.,
Dubois J. M.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.093bz.x
Subject(s) - cell growth , osmotic concentration , cell cycle , cell culture , cell , channel blocker , chemistry , cell division , patch clamp , biophysics , microbiology and biotechnology , biology , biochemistry , receptor , genetics , organic chemistry , calcium
1 A variety of studies have suggested that K + channel activity is a key determinant for cell progression through the G1 phase of mitosis. We have previously proposed that K + channels control the activity of cell cycle‐regulating proteins via regulation of cell volume. In order to test this hypothesis, we measured, with a Coulter counter and under different experimental conditions, the volume and rate of proliferation of neuroblastoma × glioma hybrid NG108‐15 cells. 2 The K + channel blockers TEA (1‐10 mM), 4‐aminopyridine (0.2‐2 mM) and Cs + (2.5‐10 mM) increased the cell volume and decreased the rate of cell proliferation. Proliferation was fully inhibited when cell volume was increased by 25 %. 3 A 40 % increase in the culture medium osmolarity with NaCl induced a 25 % increase in cell volume and an 82 % decrease in the rate of cell proliferation. A 40 % increase in the culture medium osmolarity with mannitol induced a 9 % increase in cell volume and a 60 % decrease in the rate of cell proliferation. 4 The Cl − channel blocker NPPB (5‐nitro‐2‐(3‐phenylpropylamino) benzoic acid; 50 μM) induced a 12 % increase in cell volume and a 77 % decrease in the rate of cell proliferation. 5 A 24 % reduction in the culture medium osmolarity with H 2 O induced a 21 % decrease in cell volume and a 32 % increase in the rate of cell proliferation. 6 Under whole‐cell patch‐clamp conditions, antibiotics (penicillin plus streptomycin) decreased the voltage‐dependent K + current. Omission of antibiotics from the culture medium induced a 10 % decrease in the cell volume and a 32 % increase in the rate of cell proliferation. 7 These results suggest that the mechanisms controlling cell proliferation are strongly influenced by the factors which determine cell volume. This could take into account the role in mitogenesis of K + channels and of other ionic pathways involved in cell volume regulation.