title: Mechanism of spontaneous intracellular calcium fluctuations in single GH4C1 rat pituitary cells.
abstract: Individual unstimulated GH4C1 cells exhibited spontaneous dynamic fluctuations in cytosolic free Ca2+ concentration ([Ca2+]i). Either chelation of extracellular Ca2+ with EGTA or treatment with nifedipine inhibited spontaneous [Ca2+]i fluctuations, indicating that the [Ca2+]i profile was dependent on the entry of extracellular Ca2+ via voltage-operated Ca2+ channels (VOCC). Spontaneous [Ca2+]i fluctuations did not resume immediately after exposure of EGTA-pretreated cells to extracellular Ca2+, supporting the hypothesis that the complex [Ca2+]i profiles observed in unstimulated cells required filling of an intracellular Ca2+ pool. BAY K 8644 elicited large rapid oscillations in [Ca2+]i. After chelation of extracellular Ca2+, however, re-addition of Ca2+ plus BAY K 8644 did not result in [Ca2+]i oscillations. The intracellular Ca2+ pool necessary for BAY K-induced oscillations was not the same Ins(1,4,5)P3-sensitive pool stimulated by thyrotropin-releasing hormone (TRH), because the TRH-stimulated Ins(1,4,5)P3-induced [Ca2+]i spike and the BAY K 8644-induced oscillations were differentially sensitive to chelation of extracellular Ca2+ and thapsigargin. Caffeine caused an increase in [Ca2+]i fluctuations in quiescent cells, supporting a role for Ca(2+)-induced Ca2+ release (CICR) in the generation of spontaneous [Ca2+]i fluctuations. In conclusion, the complex spontaneous changes in [Ca2+]i observed in single GH4C1 cells depend on both the influx of extracellular Ca2+ through VOCC and the action of an intracellular Ca2+ pool that increases [Ca2+]i through a CICR-like mechanism.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA.
authors.forename: K A
authors.initials: KA
authors.lastname: Wagner
authors.forename: P W
authors.initials: PW
authors.lastname: Yacono
authors.forename: D E
authors.initials: DE
authors.lastname: Golan
authors.forename: A H
authors.initials: AH
authors.lastname: Tashjian
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D008564:Membrane Potentials; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
chemical_list: D013973:Thyrotropin-Releasing Hormone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium