Roles of CRAC and Cav-like channels in T cells: more than one gatekeeper?
Ca2+ channels in the plasma membrane of T cells vitally influence Ca2+-dependent signals that lead ultimately to cytokine secretion, cellular proliferation and apoptosis. Conventional models depict the Ca2+ inrush across the T-cell membrane following T-cell receptor engagement as being due to Ca2+-release-activated Ca2+ (CRAC) channels. A poorly understood mechanism detects the lowered Ca2+ concentrations within intracellular stores that open CRAC channels. Mammalian homologs of the Drosophila transient receptor potential Ca2+ channels possibly help to gate the store-operated, Ca2+-borne CRAC current. In this article, we review evidence of a supplementary involvement of other Ca2+ channels, the opening of which does not necessarily reflect intracellular Ca2+-store depletion. We highlight a role for variants of L-type voltage-dependent Ca2+ channels in increasing intracellular Ca2+ concentrations during activation. For more-accurate modeling of lymphocyte activation and possible pharmacological interventions, future research should aim to identify physiologically relevant situations in which such channels help to shape the Ca2+ signal.
Kotturi
Maya F
MF
The Biomedical Research Centre, Michael Smith Laboratories, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada.
Hunt
Simon V
SV
Jefferies
Wilfred A
WA
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*
D015220:Calcium Channels