INHIBITION OF CELL-GROWTH BY K-INDUCED CA2+ RELEASE( CHANNEL MODULATORS IS DUE TO INTERFERENCE WITH AGONIST)

The effects of K+ channel modulators, tetraethylammonium, 4-aminopyrid ine and diazoxide, and high extracellular K+ on cell growth and agonis t-induced intracellular Ca2+ mobilization were investigated. Two human brain tumour cell lines, U-373 MG astrocytoma and SK-N-MC neuroblasto ma, were used as model cellular systems. K+ channel modulators and inc reased extracellular K+ concentration inhibited tumour cell growth in a dose-related fashion in both cell lines. In addition, agonist (carba chol or serum)-induced intracellular Ca2+ mobilization was also blocke d by the pretreatment of growth-inhibitory concentrations of K+ channe l modulators and high extracellular K+. Thus, these results suggest th at K+ channel modulators are effective inhibitors of brain tumour cell growth and that their growth regulation may be due to the interferenc e with the intracellular Ca2+ signalling mechanisms.