A non-voltage-gated calcium channel with L-type characteristics activated by B cell receptor ligation
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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.
|Number of pages||9|
|Publication status||Published - 15 Nov 2003|
- Thapsigargin, Calcium, Tumor Cells, Cultured, Humans, Calcium Channels, L-Type, Receptors, Antigen, B-Cell, Carcinogens, B-Lymphocytes, Calcium Signaling