title: Capacitative Ca2+ influx in glial cells is inhibited by glycolytic inhibitors.
abstract: In non-excitable cells, stimulation of phosphoinositide (PI) turnover and inhibition of the endoplasmic reticulum (ER) Ca2+-ATPase are methods commonly used to deplete calcium stores, resulting in a capacitative Ca2+ influx (i.e., Ca2+ release-activated Ca2+ influx). Since this Ca2+ influx in glial cells has not been thoroughly investigated, we have used C6 glioma cells as a glial cell model to study this phenomenon. On adding cyclopiazonic acid (CPA) or thapsigargin (TG) (two ER Ca2+-ATPase inhibitors) in Ca2+-free medium, only a small transient increase in intracellular Ca2+ was seen. After depletion of the stored Ca2+, a marked Ca2+ influx, followed by a prolonged plateau, was seen on re-addition of extracellular Ca2+ ions (2 mM), i.e., capacitative Ca2+ influx. A similar effect was seen on adding ATP, known to deplete the inositol triphosphate (IP3)-sensitive Ca2+ store in C6 cells. After various degrees of store depletion, the amplitude of the capacitative Ca2+ influx was found to be highly dependent on the amount of Ca2+ remaining in the store. This Ca2+ influx was markedly inhibited by (1) La3+ and Ni2+, (2) SK&F 96365, econazole, and miconazole, and (3) membrane depolarization, clearly showing that this Ca2+ influx after store depletion in C6 cells is a capacitative mechanism. Interestingly, the capacitative Ca2+ influx can be inhibited by a reduction in intracellular ATP (ATPi) levels in glial cells. The role of ATPi in the capacitative Ca2+ influx is discussed.
authors.affiliation: Institute of Physiology, College of Medicine, National Taiwan University, Taipei.
authors.forename: M L
authors.initials: ML
authors.lastname: Wu
authors.forename: E F
authors.initials: EF
authors.lastname: Kao
authors.forename: I H
authors.initials: IH
authors.lastname: Liu
authors.forename: B S
authors.initials: BS
authors.lastname: Wang
authors.forename: S Y
authors.initials: SY
authors.lastname: Lin-Shiau
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology; D011522:Protons; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D000963:Antimetabolites; D003486:Cyanides; D007093:Imidazoles; D007461:Iodoacetates; D009840:Oligomycins; D011522:Protons; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D007811:Lanthanum; D009532:Nickel; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D000252:Calcium-Transporting ATPases; D002118:Calcium; D019807:Iodoacetic Acid