Effects of inhibitors and ion substitutions on oscillations of cell membrane potential in cells expressing the RAS oncogene.
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 mmol/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 mumol/l), furosemide (1 mmol/l) and hydrochlorothiazide (100 mumol/l), by cobalt (100 mumol/l), zinc (100 mumol/l), gadolinium (100 mumol/l), verapamil (10 mumol/l) and diltiazem (10 mumol/l), but are abolished in the presence of 100 mumol/l lanthanum, 1 mmol/l cadmium, 10 mumol/l nifedipine, 25 mumol/l SK & F 96365 and 200 mumol/l TMB-8. Stimulation of calcium entry by 10 nmol/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.
Lang
F
F
Institute for Physiology, University of Innsbruck, Austria.
Waldegger
S
S
Woell
E
E
Ritter
M
M
Maly
K
K
Grunicke
H
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects*; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D011905:Genes, ras / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D013050:Spectrometry, Fluorescence; D014162:Transfection
D002121:Calcium Channel Blockers