Pflügers Archiv

, Volume 421, Issue 5, pp 416–424 | Cite as

Effects of inhibitors and ion substitutions on oscillations of cell membrane potential in cells expressing the RAS oncogene

  • F. Lang
  • S. Waldegger
  • E. Woell
  • M. Ritter
  • K. Maly
  • H. Grunicke
Transport Processes, Metabolism and Endocrinology: Kidney, Gastrointestinal Tract, and Exocrine Glands


Previous studies revealed that in NIH fibroblasts expressing the ras oncogene but not in other NIH fibroblasts, bradykinin leads to sustained, calcium dependent oscillations of cell membrane potential by repetitive activation of calcium-sensitive K+ channels. The present study has been performed to test for ion and inhibitor sensitivity of these oscillations. Both, Lys-bradykinin (kallidin) and bradykinin, but not any shorter peptide tested, maintained the oscillations. The oscillations are abolished in the presence of the K+ channel blocker barium (10 nmol/l). The amplitude but not the frequency of the oscillations is dependent on the extracellular potassium concentration. The oscillations are not dependent on the presence of extracellular sodium, bicarbonate or chloride. The oscillations are abolished in the absence of extracellular calcium and their frequency is significantly decreased at reduced extracellular calcium (to 0.2 mmol/l). The oscillations are not inhibited by acute administration of ouabain (0.1 mmol/l), by dimethylamiloride (100 μmol/l), furosemide (1 mmol/l) and hydrochlorothiazide (100 μmol/l), by cobalt (100 μmol/l), zinc (100 μmol/l), gadolinium (100 μmol/l), verapamil (10 μmol/l) and diltiazem (10 μmol/l), but are abolished in the presence of 100 μmol/l lanthanum, 1 mmol/l cadmium, 10 μmol/l nifedipine, 25 μmol/l SK & F 96365 and 200 μmol/l TMB-8. Stimulation of calcium entry by 10 μmol/l ionomycin is frequently followed by oscillations of cell membrane potential even in the absence of bradykinin. In conclusion, in cells expressing the ras oncogene bradykinin leads to sustained activation of calcium channels at the cell membrane, which cause oscillations of the cell membrane potential by triggering intracellular calcium release.

Key words

ras oncogene Cell membrane potential Ca2+ channels K+ channels Bradykinin 


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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • F. Lang
    • 1
  • S. Waldegger
    • 1
  • E. Woell
    • 1
  • M. Ritter
    • 1
  • K. Maly
    • 2
  • H. Grunicke
    • 2
  1. 1.Institute for PhysiologyUniversity of InnsbruckInnsbruckAustria
  2. 2.Institute for BiochemistryUniversity of InnsbruckInnsbruckAustria

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