Evidence for a receptor-activated Ca2+ entry pathway independent from Ca2) store depletion in endothelial cells.
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.
Jousset
H
H
Department of Cell Physiology and Metabolism, Geneva Medical Center, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
Malli
R
R
Girardin
N
N
Graier
W F
WF
Demaurex
N
N
Frieden
M
M
D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D019069:Cell Respiration / Q000187:drug effects; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D011956:Receptors, Cell Surface; D007811:Lanthanum; D006632:Histamine; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium