A quantitative analysis of the role of K+ channels in mitogenesis of neuroblastoma cells.
The role of K+ channels in mitogenesis was studied on mouse neuroblastoma cells by analysing the effects of various chemical agents on the whole-cell K+ current and the cell proliferation. The outward current recorded during depolarizations on undifferentiated cells was made up of a small and slow inactivating K+ current. Foetal calf serum, which is mitogen for neuroblastoma cells, shifted in opposite directions by 7-10 mV peak activation and steady-state inactivation-voltage curves of the K+ current. The resulting effect was an increase in K+ conductance. The effect on the resting K+ flux of the classical K+ channel blockers tetraethylammonium, 4-aminopyridine and capsaicin, the anticancer agent tamoxifen, the heat inactivated serum and the increase in external K+ concentration were estimated from their effects on the K+ current. The cell proliferation was determined under the same conditions. The results indicate that cell proliferation is correlated to the resulting K+ flux. It is supposed that mitogenesis is controlled by the intracellular Na+ concentration which, via a cell volume regulation, is a function of the K+ flux. A quantitative model is developed on the basis of these hypotheses.
Rouzaire-Dubois
B
B
Laboratoire de Physiologie Comparée, URA CNRS 1121, Université Paris-Sud, Orsay, France.
Dubois
J M
JM
D002455:Cell Division / Q000502:physiology*; D004563:Electrochemistry; D008934:Mitogens; D009447:Neuroblastoma; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D008934:Mitogens; D015221:Potassium Channels