Sodium channel activation does not alter lipid metabolism in cultured neuroblastoma cells.
The interaction of voltage-sensitive Na+-channels and membrane lipid metabolism was examined by incubating cultured neuroblastoma cells with neurotoxins which alter the voltage-dependent relationship between the closed and open conformation of the channel protein. Guanidinium flux rate, a measure of Na+-channel activation, was increased 10-fold by the combined action of veratridine (100 microM) and scorpion venom (28 micrograms/ml). This response was completely blocked by tetrodotoxin (1 microM). Under the same experimental conditions, the toxins did not increase the efflux of [3H]arachidonic acid from prelabeled cell membrane lipids or stimulate uptake of exogenous [3H]arachidonic acid. In addition, altering membrane fatty acid composition by incubating cells for 24 hr in a medium containing 50 microM arachidonic or oleic acid did not alter guanidinium flux rates relative to that of control cultures. When cells were pulsed with 32Pi for 60 min and stimulated by veratridine plus scorpion venom for an additional 30 min, uptake of 32Pi into phosphatidylinositol was reduced; stimulating cells with bradykinin, a receptor agonist which activates the inositol cycle, promoted a 3.8 fold increase. Polyphosphoinositide turnover was not affected by Na+-channel activation, but was stimulated by bradykinin. These results suggest that voltage-sensitive Na+-channel activation in cultured neuroblastoma cells can function independent of membrane phospholipid and fatty acid metabolism.
Glanville
T N
TN
Atlantic Research Center for Mental Retardation, Halifax, Nova Scotia, Canada.
Spence
M W
MW
Cook
H W
HW
Palmer
F B
FB
D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D009447:Neuroblastoma; D009498:Neurotoxins / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D001095:Arachidonic Acids; D008563:Membrane Lipids; D009498:Neurotoxins; D010743:Phospholipids; D015222:Sodium Channels; D014701:Veratridine; D001920:Bradykinin