Effect of calcium channel antagonists on cell membrane potential oscillations and proliferation of cells expressing the ras oncogene

Eur J Pharmacol. 1992 Feb 25;212(1):105-7. doi: 10.1016/0014-2999(92)90080-n.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Bradykinin / pharmacology
  • Calcium Channel Blockers / pharmacology*
  • Cell Division / drug effects*
  • Diltiazem / pharmacology
  • Gene Expression
  • Genes, ras*
  • Membrane Potentials / drug effects*
  • Mice
  • Nifedipine / pharmacology
  • Transfection
  • Verapamil / pharmacology

Substances

  • Calcium Channel Blockers
  • Verapamil
  • Diltiazem
  • Nifedipine
  • Bradykinin