A non-voltage-gated calcium channel with L-type characteristics activated by B cell receptor ligation

Gillian Grafton, Leanne Stokes, Kai-Michael Toellner, John Gordon

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)2001-9
Number of pages9
JournalBiochemical Pharmacology
Volume66
Issue number10
DOIs
Publication statusPublished - 15 Nov 2003

Keywords

  • Thapsigargin
  • Calcium
  • Tumor Cells, Cultured
  • Humans
  • Calcium Channels, L-Type
  • Receptors, Antigen, B-Cell
  • Carcinogens
  • B-Lymphocytes
  • Calcium Signaling

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