Cell shrinkage stimulates bradykinin-induced cell membrane potential oscillations in NIH 3T3 fibroblasts expressing the ras-oncogene

• Published in: Pflügers Archiv Vol. 423; no. 3-4; p. 221
• Main Authors: Ritter, M, Wöll, E, Waldegger, S, Häussinger, D, Lang, H J, Scholz, W, Schölkens, B, Lang, F
• Format: Journal Article
• Language: English
• Published: Germany 01.05.1993
• Subjects: 3T3 Cells; Animals; Bradykinin - pharmacology; Calcium - metabolism; Cell Membrane - physiology; Cell Size - drug effects; Gene Expression; Genes, ras; Hydrogen-Ion Concentration; Membrane Potentials - drug effects; Mice; Osmolar Concentration; Sodium Chloride - pharmacology
• ISSN: 0031-6768
• DOI: 10.1007/BF00374398

In NIH 3T3 fibroblasts expressing the Ha-ras oncogene (+ ras) bradykinin leads to sustained oscillations of cell membrane potential due to oscillations of intracellular Ca2+ with subsequent activation of Ca(2+)-sensitive K+ channels. In cells not expressing the oncogene (-ras), bradykinin leads only to a single transient hyperpolarization of the cell membrane. The present study has been performed to elucidate the possible interaction of cell volume, intracellular pH and bradykinin-induced oscillations of the cell membrane potential. Bradykinin leads to cell shrinkage and intracellular alkalinization of both + ras cells and -ras cells. Inhibition of Na+/H+ exchanger by HOE 694 abolishes the bradykinin-induced alkalinization but does not significantly interfere with the bradykinin-induced oscillations of cell membrane potential. In contrast, prevention of bradykinin-induced cell shrinkage by simultaneous reduction of extracellular osmolarity blunts the oscillations. Thus, cell shrinkage stimulates bradykinin-induced oscillations of cell membrane potential. On the other hand, cell shrinkage alone does not elicit oscillations unless, in addition, Ca2+ entry is stimulated by ionomycin.