Mechanism of intracellular calcium oscillations in fibroblasts expressing the ras oncogene.

In NIH fibroblasts expressing the ras oncogene bradykinin leads to sustained, calcium-dependent oscillations of cell membrane potential by oscillating activity of calcium sensitive potassium channels. The present study has been performed to further analyse the underlying mechanisms. In cells expressing the oncogene, but not in NIH fibroblasts not expressing the oncogene, bradykinin elicits calcium oscillations, which are detected by fura-2 fluorescence and amplified by a decrease of extracellular sodium activity. These calcium oscillations are dependent on the presence of extracellular calcium and are inhibited by lanthanum ions. It is concluded that in cells expressing the ras oncogene, bradykinin activates lanthanum sensitive calcium entry from the extracellular space. Ras oncogene expression leads to enhanced bradykinin-induced formation of both, 1, 4, 5 inositoltrisphosphate and 1, 3, 4, 5 inositoltetrakisphosphate, an effect probably accounting for the oscillations of intracellular calcium activity.