Cell shrinkage stimulates bradykinin-induced cell membrane potential oscillations in NIH 3T3 fibroblasts expressing the ras-oncogene.
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.
Ritter
M
M
Physiologisches Institut, Universität Innsbruck, Austria.
Wöll
E
E
Waldegger
S
S
Häussinger
D
D
Lang
H J
HJ
Scholz
W
W
Schölkens
B
B
Lang
F
F
D016475:3T3 Cells; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D048429:Cell Size / Q000187:drug effects*; D015870:Gene Expression; D011905:Genes, ras; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D009994:Osmolar Concentration; D012965:Sodium Chloride / Q000494:pharmacology
D012965:Sodium Chloride; D001920:Bradykinin; D002118:Calcium