Inhibition of cell growth by K+ channel modulators is due to interference with agonist-induced Ca2+ release.

The effects of K+ channel modulators, tetraethylammonium, 4-aminopyridine and diazoxide, and high extracellular K+ on cell growth and agonist-induced intracellular Ca2+ mobilization were investigated. Two human brain tumour cell lines, U-373 MG astrocytoma and SK-N-MC neuroblastoma, were used as model cellular systems. K+ channel modulators and increased extracellular K+ concentration inhibited tumour cell growth in a dose-related fashion in both cell lines. In addition, agonist (carbachol or serum)-induced intracellular Ca2+ mobilization was also blocked by the pretreatment of growth-inhibitory concentrations of K+ channel modulators and high extracellular K+. Thus, these results suggest that K+ channel modulators are effective inhibitors of brain tumour cell growth and that their growth regulation may be due to the interference with the intracellular Ca2+ signalling mechanisms.