Gap junctional communication modulates agonist-induced calcium oscillations in transfected HeLa cells.
Gap junctional communication modulates intercellular calcium signaling in many cell types. We have investigated whether gap junctional communication modulates calcium oscillatory behavior of cells responding to an agonist. Extracellular UTP induced calcium oscillations in 70% of HeLa cells cultured in monolayer, and neighboring cells oscillated independently of each other. In HeLa cell transfectants expressing connexin43 (HeLa/Cx43), extracellular UTP induced calcium transients, but calcium oscillations occurred in only 10% of cells. Inhibition of gap junctional communication with anandamide in HeLa/Cx43 transfectants substantially restored oscillations (55% of cells). In HeLa/Cx45 transfectants, UTP initiated calcium oscillations similar to those seen in HeLa cells (63% of cells), but HeLa/Cx46 transfectants demonstrated calcium oscillations that were dampened compared to those of the parental HeLa cells, and occurred in only 40% of cells. These experiments demonstrate that gap junctional communication modulates calcium oscillatory behavior in cell monolayers, presumably by allowing cells to share a small molecule such as inositol trisphosphate. These studies suggest that gap junctional communication may alter the nature of signals induced by calcium mobilizing agonists in a connexin-dependent fashion by modulating calcium oscillatory behavior.
Lin
George C
GC
Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Rurangirwa
Jacqueline K
JK
Koval
Michael
M
Steinberg
Thomas H
TH
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D063388:Endocannabinoids; D017629:Gap Junctions / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D051379:Mice; D053284:Polyunsaturated Alkamides; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014544:Uridine Triphosphate / Q000494:pharmacology
D001095:Arachidonic Acids; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017630:Connexins; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; C078814:anandamide; D014544:Uridine Triphosphate