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Calmidazolium and arachidonate activate a calcium entry pathway that is distinct from store-operated calcium influx in HeLa cells

Authors
 Claire M. PEPPIATT  ;  Anthony M. HOLMES  ;  H. Llewelyn RODERICK  ;  Fraser McMDONALD  ;  Tony J. COLLINS  ;  Martin D. BOOTMAN  ;  Jeong T. SEO 
Citation
 BIOCHEMICAL JOURNAL, Vol.381(3) : 929-939, 2004 
Journal Title
BIOCHEMICAL JOURNAL
ISSN
 0264-6021 
Issue Date
2004
MeSH
Arachidonic Acid/metabolism* ; Calcium/metabolism* ; Calcium Channels/metabolism* ; Calcium Signaling/drug effects ; Calcium Signaling/physiology ; Calmodulin/antagonists & inhibitors ; Calmodulin/physiology ; Cell Line, Tumor ; Cytosol/chemistry ; HeLa Cells/chemistry ; HeLa Cells/metabolism* ; Humans ; Imidazoles/metabolism* ; Sulfonamides/pharmacology ; Trifluoperazine/pharmacology
Keywords
arachidonic acid ; calcium ; calmidazolium ; calmodulin ; inositol ; phospholipase
Abstract
Agonists that deplete intracellular Ca2+ stores also activate Ca2+ entry, although the mechanism by which store release and Ca2+ influx are linked is unclear. A potential mechanism involves 'store-operated channels' that respond to depletion of the intracellular Ca2+ pool. Although SOCE (store-operated Ca2+ entry) has been considered to be the principal route for Ca2+ entry during hormonal stimulation of non-electrically excitable cells, recent evidence has suggested that alternative pathways activated by metabolites such as arachidonic acid are responsible for physiological Ca2+ influx. It is not clear whether such messenger-activated pathways exist in all cells, whether they are truly distinct from SOCE and which metabolites are involved. In the present study, we demonstrate that HeLa cells express two pharmacologically and mechanistically distinct Ca2+ entry pathways. One is the ubiquitous SOCE route and the other is an arachidonate-sensitive non-SOCE. We show that both these Ca2+ entry pathways can provide long-lasting Ca2+ elevations, but that the channels are not the same, based on their differential sensitivity to 2-aminoethoxydiphenyl borate, LOE-908 [(R,S)-(3,4-dihydro-6,7-dimethoxy-isochinolin-1-yl)-2-phenyl-N,N-di[2-(2,3,4-trimethoxyphenyl)ethyl]acetamid mesylate] and gadolinium. In addition, non-SOCE and not SOCE was permeable to strontium. Furthermore, unlike SOCE, the non-SOCE pathway did not require store depletion and was not sensitive to displacement of the endoplasmic reticulum from the plasma membrane using jasplakinolide or ionomycin pretreatment. These pathways did not conduct Ca2+ simultaneously due to the dominant effect of arachidonate, which rapidly curtails SOCE and promotes Ca2+ influx via non-SOCE. Although non-SOCE could be activated by exogenous application of arachidonate, the most robust method for stimulation of this pathway was application of the widely used calmodulin antagonist calmidazolium, due to its ability to activate phospholipase A2.
Files in This Item:
T200401698.pdf Download
DOI
10.1042/BJ20040097
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/112766
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