A non-voltage-gated calcium channel with L-type characteristics activated by B cell receptor ligation.
In mature B cells engagement of the antigen-receptor (BCR) results in a peak of Ca(2+) from mobilisation of internal stores followed by a lower but sustained elevation that is dependent upon extracellular Ca(2+). The Ca(2+) channel involved in the sustained elevation remains uncharacterised. Here we have presented evidence that although non-excitable, B cells expressed a BCR-activated Ca(2+) channel sharing some properties of conventional L-type voltage-gated channels. Human lymphoma B cells expressed a transcript having homology to a highly conserved region on the pore-forming alpha(1.2) subunit of L-type voltage-gated Ca(2+) channels. The alpha(1.2) protein was expressed together with the beta1 subunit, while an antibody raised against the extracellular portion of L-type Ca(2+) channels caused a Ca(2+) flux in these cells. Drugs that block classical L-type channels abolished the BCR-induced Ca(2+) flux while directly activating a plasma membrane Ca(2+) channel: activation of the channel, separate from Ca(2+) influx, inhibited BCR-induced Ca(2+) release from intracellular stores. BAYK8644-a drug that binds to open L-type channels-failed to release intracellular Ca(2+) in the absence of BCR cross-linking but instantly abolished the BCR-induced Ca(2+) peak and established the sustained phase of the response. The BCR-activated calcium channel appeared to terminate the initial peak of BCR-induced Ca(2+) release and initiate the sustained phase of the signal.
MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham B15 2TT, Edgbaston, UK. G.Grafton@bham.ac.uk
Gillian
G
Grafton
Leanne
L
Stokes
Kai Michael
KM
Toellner
John
J
Gordon
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002273:Carcinogens / Q000494:pharmacology; D006801:Humans; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020746:Calcium Channels, L-Type; D002273:Carcinogens; D011947:Receptors, Antigen, B-Cell; D019284:Thapsigargin; D002118:Calcium