title: Extracellular calcium concentration controls the frequency of intracellular calcium spiking independently of inositol 1,4,5-trisphosphate production in HeLa cells.
abstract: Stimulation of single HeLa cells with histamine evoked repetitive increases of the intracellular calcium ion concentration (Ca2+ spikes). The frequency of Ca2+ spiking increased as the extracellular hormone concentration was elevated. In addition, the frequency of Ca2+ spiking could be accelerated by increasing the extracellular Ca2+ concentration ([Ca2+]0) in the presence of a constant hormone concentration. The range of [Ca2+]0 over which the spiking frequency could be titrated was nominally-zero to 10mM, being half-maximally effective at approx. 1 and 2.5mM for 37 and 22 degrees C respectively. The effect of [Ca2+]0 on inositol phosphates production was also examined. Changes of [Ca2+]0 over a range which had been found to affect the frequency of Ca2+ spiking did not have any effect on the rate of myo-inositol 1,4,5-trisphosphate (InsP3) production, although an increase in inositol phosphates production was observed as [Ca2+]0 was increased from zero to values giving less than half-maximal Ca2+ spike frequency. These data suggest that at low Ca2+ spike frequency, Ca2+-stimulated activation of phospholipase C may contribute to Ca2+ spiking in HeLa cells, but under some conditions the availability of Ca2+ to the intracellular stores, rather than changes in the rate of InsP3 production, determines the Ca2+ spike frequency.
authors.affiliation: The Babraham Institute Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, U.K.
authors.forename: M D
authors.initials: MD
authors.lastname: Bootman
authors.forename: K W
authors.initials: KW
authors.lastname: Young
authors.forename: J M
authors.initials: JM
authors.lastname: Young
authors.forename: R B
authors.initials: RB
authors.lastname: Moreton
authors.forename: M J
authors.initials: MJ
authors.lastname: Berridge
mesh_terms: D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D005453:Fluorescence; D016257:Fura-2 / Q000378:metabolism; D006367:HeLa Cells; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D007295:Inositol Phosphates; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2