Evidence for a receptor-activated Ca2+ entry pathway independent from Ca2+ store depletion in endothelial cells

Autor: Nathalie C Girardin, Maud Frieden, Nicolas Demaurex, Wolfgang F. Graier, Roland Malli, Hélène Jousset
Rok vydání: 2008
Předmět:
Calcium Channel Blockers/pharmacology
Histamine/pharmacology
Agonist
Calcium/metabolism
SERCA
Calcium Channels/metabolism
Physiology
medicine.drug_class
Cell Respiration
Mitochondria/drug effects/metabolism
Receptors
Cell Surface
Stimulation
Endoplasmic Reticulum
Article
chemistry.chemical_compound
Lanthanum
Cell Respiration/drug effects
medicine
Extracellular
Humans
Calcium Signaling
ddc:612
Receptor
Endoplasmic Reticulum/metabolism
Molecular Biology
Cells
Cultured
Imidazoles/pharmacology
Receptors Cell Surface/metabolism
Chemistry
Biological Transport/drug effects
Endoplasmic reticulum
Imidazoles
Endothelial Cells
Biological Transport
Depolarization
Cell Biology
Calcium Channel Blockers
Mitochondria
Cell biology
Endothelial Cells/drug effects/metabolism
Calcium
Calcium Channels
Cells Cultured
Lanthanum/pharmacology
Histamine
Zdroj: Cell Calcium, Vol. 43, No 1 (2008) pp. 83-94
ISSN: 0143-4160
DOI: 10.1016/j.ceca.2007.04.006
Popis: Ca(2+) entry in endothelial cells is a key signaling event as it prolongs the Ca(2+) signal activated by a receptor agonist, and thus allows an adequate production of a variety of compounds. The possible routes that lead to Ca(2+) entry in non-excitable cells include the receptor-activated Ca(2+) entry (RACE), which requires the presence of an agonist to be activated, and the store-operated Ca(2+) entry (SOCE) pathway, whose activation requires the depletion of the ER Ca(2+) store. However, the relative importance of these two influx pathways during physiological stimulation is not known. In the present study we experimentally differentiated these two types of influxes and determined under which circumstances they are activated. We show that La(3+) (at 10 microM) is a discriminating compound that efficiently blocks SOCE but is almost without effect on histamine-induced Ca(2+) entry (RACE). In line with this, histamine does not induce massive store depletion when performed in the presence of extracellular Ca(2+). In addition, inhibition of mitochondrial respiration significantly reduces SOCE but modestly affects RACE. Thus, agonist-induced Ca(2+) entry is insensitive to La(3+), and only modestly affected by mitochondrial depolarization. These data shows that agonist relies almost exclusively on RACE for sustained Ca(2+) signaling in endothelial cells.
Databáze: OpenAIRE
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