Cell membrane potential oscillations induced by kinins in fibroblasts expressing the Ha-ras oncogene.
In NIH-3T3 fibroblasts expressing the ras oncogene (+ras) bradykinin (BK) elicits sustained oscillations (1/min) of cell membrane potential (PD) due to oscillations of intracellular calcium activity with subsequent activation of calcium sensitive K+ channels. In NIH-3T3 fibroblasts not expressing the oncogene (-ras), BK leads to a single transient hyperpolarization of the cell membrane, not followed by oscillations. The oscillations of cell membrane potential require the presence of extracellular calcium and are abolished by K+ channel blocker barium (1 mmol/l), as well as by calcium channel blockers cadmium (1 mmol/l), lanthanum (0.1 mmol/l) and nifedipine (10 mumol/l). However, the oscillations are not modified by 1 mumol/l nifedipine, or by other calcium channel blockers, such as verapamil (10 mumol/l) or diltiazem (10 mumol/l). Cell proliferation is inhibited by nifedipine (10 mumol/l) but not by verapamil or diltiazem, indicating that the oscillations of intracellular calcium are a prerequisite for the growth factor independent proliferation of ras oncogene expressing cells.
Lang
F
F
Institute for Physiology, University of Innsbruck, Austria.
Wöll
E
E
Waldegger
S
S
Friedrich
F
F
Ritter
M
M
Pinggera
G
G
Kloiber
K
K
Bichler
I
I
Heitzenberger
H
H
Maly
K
K
D016475:3T3 Cells; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000502:physiology; D011905:Genes, ras; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D014162:Transfection
D002121:Calcium Channel Blockers; D001464:Barium; D001920:Bradykinin; D002118:Calcium