Cell membrane potential oscillations induced by kinins in fibroblasts expressing the Ha-ras oncogene.

In NIH-3T3 fibroblasts expressing the ras oncogene (+ras) bradykinin (BK) elicits sustained oscillations (1/min) of cell membrane potential (PD) due to oscillations of intracellular calcium activity with subsequent activation of calcium sensitive K+ channels. In NIH-3T3 fibroblasts not expressing the oncogene (-ras), BK leads to a single transient hyperpolarization of the cell membrane, not followed by oscillations. The oscillations of cell membrane potential require the presence of extracellular calcium and are abolished by K+ channel blocker barium (1 mmol/l), as well as by calcium channel blockers cadmium (1 mmol/l), lanthanum (0.1 mmol/l) and nifedipine (10 mumol/l). However, the oscillations are not modified by 1 mumol/l nifedipine, or by other calcium channel blockers, such as verapamil (10 mumol/l) or diltiazem (10 mumol/l). Cell proliferation is inhibited by nifedipine (10 mumol/l) but not by verapamil or diltiazem, indicating that the oscillations of intracellular calcium are a prerequisite for the growth factor independent proliferation of ras oncogene expressing cells.