Arachidonic acid inhibits capacitative Ca2+ entry and activates non-capacitative Ca2+ entry in cultured astrocytes.
Arachidonic acid (AA) plays important physiological or pathophysiological roles. Here, we show in cultured rat astrocytes that: (i) endothelin-1 or thapsigargin (Tg) induces store-depleted activated Ca(2+) entry (CCE), which is inhibited by 2-aminoethoxydiphenyl borane (2-APB) or La(3+); (ii) AA (10 microM) and other unsaturated fatty acids (8,11,14-eicosatrienoic acid and gamma-linoleic acid) have an initial inhibitory effect on the CCE, due to AA- or fatty acid-induced internal acid load; (iii) after full activation of CCE, AA induces a further Ca(2+) influx, which is not inhibited by 2-APB or La(3+), indicating that AA activates a second Ca(2+) entry pathway, which coexists with CCE; and (iv) Tg or AA activates two independent and co-existing non-selective cation channels and the Tg-induced currents are initially inhibited by addition of AA or weak acids. A possible pathophysiological effect of the AA-induced [Ca](i) overload is to cause delayed cell death in astrocytes.
Yang
Kun-Ta
KT
Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Wen-Pin
WP
Chang
Wei-Luen
WL
Su
Ming-Jai
MJ
Tsai
Ke-Li
KL
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D025802:Electric Capacitance; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects*; D008345:Manganese / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology
D016718:Arachidonic Acid; D008345:Manganese; D019284:Thapsigargin; D002118:Calcium