Ca2+ entry in T cells is activated by emptying the inositol 1,4,5-triphosphate sensitive Ca2+ pool.
Using alpha-linolenic acid (ALA), one of several polyunsaturated fatty acids (PUFAs) that have previously been shown to both mobilize intracellular Ca2+ from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ pool independently of IP3 production and inhibit Ca2+ influx, the relationship between Ca2+ mobilization from intracellular stores and Ca2+ influx in T cells (JURKAT) was studied. JURKAT cells were treated with 30 microM ALA to deplete the IP3-sensitive Ca2+ pool. When the intracellular free Ca2+ concentration [( Ca2+]i) returned to basal level, fatty acid free bovine serum albumin (BSA) was added to remove extracellular and membrane bound ALA. This resulted in a sustained increase in [Ca2+]i in the absence of inositol phosphates' formation. This sustained increase in [Ca2+]i was insensitive to protein kinase C activation but was inhibited by Ni2+ ions. The extent of Ca2+ influx was found to be correlated to the amount of Ca2+ initially discharged from the IP3-sensitive Ca2+ pool by sub-optimal concentrations of ALA. Ligation of the CD3 complex of the T cell antigen receptor with an anti-CD3 antibody (OKT3) during the sustained [Ca2+]i increased (induced by a sub-optimal concentration of ALA), produced a greater response. No increase in the sustained response was observed when the CD3 complex was activated in cells pretreated with an optimal concentration of ALA. In summary, Ca2+ entry in T cells is activated by emptying of the IP3-sensitive Ca2+ pool which can be dissociated from inositol phosphate production. The rate of Ca2+ influx appears to be closely correlated to the initial discharge of Ca2+ from the IP3-sensitive Ca2+ pool, suggesting that Ca2+ may first enter the depleted pool and then is released into the cytosol.
Chow
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SC
Department of Immunology, Karolinska Institute, Stockholm, Sweden.
Jondal
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D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002462:Cell Membrane / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008042:Linolenic Acids / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013050:Spectrometry, Fluorescence / Q000379:methods; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002121:Calcium Channel Blockers; D008042:Linolenic Acids; D012710:Serum Albumin, Bovine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium