Distinct mechanisms for Ca2+ entry induced by OKT3 and Ca2+ depletion in Jurkat T cells.
Ca2+ influx triggered by antigen binding to T cell receptors (TCR) is an early event in T cell activation. An additional Ca2+ influx induced by depletion of intracellular Ca2+ (CDCI) has been characterized in human Jurkat T cells that is both temporally and mechanistically distinct from TCR-mediated Ca2+ influx (TCRCI). Both TCRCI and CDCI were insensitive to voltage-gated Ca2+ channel antagonists (e.g., nifedipine, verapamil, and omega-conotoxin G) and pertussis toxin, yet were voltage-sensitive and inhibited by SKF 96365 (a receptor-gated Ca2+ channel blocker) and cholera toxin. However, TCRCI but not CDCI was associated with a significant increase in inositol phosphate (IP chi) levels and inhibited by phorbol ester, while CDCI but not TCRCI was inhibited by Sr2+, forskolin (FSK), and 1,9-dideoxy FSK in a cAMP-independent fashion. Moreover, TCR stimulation did not deplete thapsigargin-sensitive Ca2+ stores, suggesting that TCRCI is not merely a consequence of Ca2+ depletion. These results indicate that Ca2+ entry following the depletion of intracellular Ca2+ stores or TCR stimulation occur through distinct cellular mechanisms coexisting in Jurkat T cells.
Sei
Y
Y
Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, Maryland 20892.
Takemura
M
M
Gusovsky
F
F
Skolnick
P
P
Basile
A
A
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002413:Cations, Divalent / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D017136:Ion Transport; D008213:Lymphocyte Activation / Q000502:physiology; D016853:Muromonab-CD3; D037342:Pertussis Toxin; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D007295:Inositol Phosphates; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D002772:Cholera Toxin; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate; C047983:1,9-dideoxyforskolin; D002118:Calcium