Effect of calcium channel antagonists on cell membrane potential oscillations and proliferation of cells expressing the ras oncogene.
NIH fibroblasts expressing the Ha-ras oncogene (+ras), unlike otherwise identical cells not expressing the oncogene (-ras), are able to grow in serum-depleted media (0.5% fetal calf serum). Electrophysiological experiments revealed that in +ras fibroblasts but not in -ras fibroblasts, bradykinin leads to sustained, calcium-dependent oscillations of cell membrane potential by repetitive activation of calcium-sensitive K+ channels, resulting from oscillating intracellular calcium activity. The present study was performed to test for an effect of calcium channel antagonists on these phenomena. Whereas 10 mumol/l verapamil and 10 mumol/l diltiazem did not significantly interfere with either oscillations or proliferation, 10 mumol/l nifedipine completely abolished both the oscillations and the proliferation of +ras fibroblasts. The number of -ras fibroblasts remained virtually constant in both the presence and absence of 10 mumol/l nifedipine. These observations show the antiproliferative action of nifedipine and suggest that the oscillations of cell membrane potential are pertinent for the proliferation of +ras cells in serum-depleted media.
Wöll
E
E
Institute for Physiology, University of Innsbruck, Austria.
Weiss
H
H
Waldegger
S
S
Lang
F
F
D016475:3T3 Cells; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D015870:Gene Expression; D011905:Genes, ras; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D014162:Transfection; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D001920:Bradykinin