Inhibition of maitotoxin-induced Ca2+ influx in rat glioma C6 cells by brevetoxins and synthetic fragments of maitotoxin

Keiichi Konoki, Masaki Hashimoto, Taro Nonomura, Makoto Sasaki, Michio Murata, Kazuo Tachibana

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

45Ca2+ influx in rat glioma C6 cells induced by 0.3 nM maitotoxin (MTX) was markedly inhibited by brevetoxin A (PbTx1) and brevetoxin B (PbTx2), with EC50 values of 16 and 13 μM, respectively. This inhibition was observed immediately after addition of MTX when monitored with fura-2, which suggests that PbTx2 directly blocks the action of MTX. This blockade by PbTx2 was not affected by tetrodotoxin, which excludes the involvement of voltage-sensitive sodium channels. The depolarizing effects of these bravetoxins were also not a likely cause of this inhibition, because melittin, a channel-forming peptide, did not significantly block MTX-induced 45Ca2+ influx. Instead, this inhibition was thought to be mediated by blockade of an MTX-binding site by the brevetoxins, based on the fact that these toxins, particularly PbTx2 closely mimic the partial structure of MTX. Synthetic fragments of MTX corresponding to the hydrophilic EF-GH rings (200 μM) and LM-NO rings (500 μM) of MTX significantly reduced MTX-elicited Ca2+ influx. The observation that the effects of MTX were inhibited by structural mimics of both its hydrophobic and hydrophilic portions implies that both portions of the MTX molecule recognize its target.

Original languageEnglish
Pages (from-to)409-416
Number of pages8
JournalJournal of Neurochemistry
Volume70
Issue number1
DOIs
Publication statusPublished - 1998 Jan

Keywords

  • Brevetoxin
  • Maitotoxin
  • Polyether compounds
  • Rat glioma C6 cells
  • Synthetic fragments
  • Voltage-sensitive calcium channel

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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