Relationship between extracellular osmolarity, NaCl concentration and cell volume in rat glioma cells

International audienceThe cell volume, which controls numerous cellular functions, is theoretically linearly related with the inverse osmolarity. However, deviations from this law have often been observed. In order to clarify the origin of these deviations we electronically measured the mean cell volume of rat glioma cells under three different experimental conditions, namely: at different osmolarities and constant NaCl concentration; at different NaCl concentrations and constant osmolarity and at different osmolarities caused by changes in NaCl concentration. In each condition, the osmolarity was maintained constant or changed with NaCl or mannitol. We showed that the cell volume was dependent on both the extracellular osmolarity and the NaCl concentration. The relationship between cell volume, osmolarity and NaCl concentration could be described by a new equation that is the product of the Boyle-van't Hoff law and the Michaelis-Menten equation at a power of 4. Together, these results suggest that in hyponatriemia, the cell volume deviates from the Boyle-van't Hoff law because either the activity of aquaporin 1, expressed in glioma cells, is decreased or the reduced NaCl influx decreases the osmotically obliged influx of water

The Eag potassium channel as a new prognostic marker in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K⁺) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression.</p> <p>Objectives</p> <p>To determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation.</p> <p>Methods</p> <p>The expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3).</p> <p>Results</p> <p>We show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016) unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014) and presence of residual disease (P = 0.011). Proliferation of SK-OV-3 cells was significantly (P < 0.001) inhibited after treatment with voltage gated K⁺channel blockers.</p> <p>Conclusion</p> <p>This novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer.</p

Eag and HERG potassium channels as novel therapeutic targets in cancer

Voltage gated potassium channels have been extensively studied in relation to cancer. In this review, we will focus on the role of two potassium channels, Ether à-go-go (Eag), Human ether à-go-go related gene (HERG), in cancer and their potential therapeutic utility in the treatment of cancer. Eag and HERG are expressed in cancers of various organs and have been implicated in cell cycle progression and proliferation of cancer cells. Inhibition of these channels has been shown to reduce proliferation both in vitro and vivo studies identifying potassium channel modulators as putative inhibitors of tumour progression. Eag channels in view of their restricted expression in normal tissue may emerge as novel tumour biomarkers

Excitatory amino acidergic pathways and receptors in the basal ganglia

The striatum receives the majority of excitatory amino acidergic input to the basal ganglia from neocortical and allocortical sources. The subthalamic nucleus and the substantia nigra also receive excitatory amino acidergic inputs from neocortex. The subthalamic nucleus, which has prominent projections to the pallidum and nigra, is the only known intrinsic excitatory amino acidergic component of the basal ganglia. Possible excitatory amino acidergic inputs reach the basal ganglia from the intralaminar thalamic nuclei and the pedunculo-pontine nucleus. The striatum is richly endowed with all subtypes of excitatory amino acid receptors and these appear to be inhomogeneously distributed within the striatal complex. The non-striatal nuclei contain lesser levels of excitatory amino acid receptors and the relative proportion of these receptors varies between nuclei. The presence of high densities of excitatory amino acid receptors is a phylogenetically conserved feature of the striatum and its non-mammalian homologues. In Huntington's disease, there is substantial depletion of α -amino-3-hydroxy-5-methylisoxazole-4-propionic acid, N-methyl-D-aspartate, and kainate receptors within the striatum. In Parkinson's disease substantia nigra, there is significant loss of N-methyl-D-aspartate and α -amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41734/1/726_2004_Article_BF00814003.pd

K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation

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.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 %.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.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.A 24 % reduction in the culture medium osmolarity with H2O induced a 21 % decrease in cell volume and a 32 % increase in the rate of cell proliferation.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.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