Products of heme-catalyzed transformation of the arachidonate derivative 12-HPETE open S-type K+ channels in Aplysia

Francesco Belardetti, William B. Campbell, J R Falck, Giancarlo Demontis, Mark Rosolowsky

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

In Aplysia mechanosensory neurons, the neuropeptide FMRFamide increases the opening of the background S-K+ channel. This action is mediated by activation of arachidonic acid metabolism. Arachidonic acid in Aplysia nervous tissue is transformed through the 12-li-poxygenase pathway to 12-HPETE, which undergoes further metabolism. In intact sensory cells, 12-HPETE simulates the FMRFamide response, raising the question of whether 12-HPETE is the messenger molecule ultimately acting on the S-K+ channel. Here we show that in cell-free (inside-out) patches from sensory cells, 12-HPETE fails to modulate the S-K+ channel, but in the presence of hematin (which catalyzes 12-HPETE metabolism), it triggers sharp increases in the channel opening probability. We also found that SKF525A, an inhibitor of the cytochrome P450, reduces the response to FMRFamide, arachidonic acid, and 12-HPETE in intact cells. We conclude that a heme-catalyzed transformation of 12-HPETE is necessary and sufficient to promote the opening of the S-K+ channel and a hemecontaining enzyme such as cytochrome P450, might play this key role.

Original languageEnglish (US)
Pages (from-to)497-505
Number of pages9
JournalNeuron
Volume3
Issue number4
DOIs
StatePublished - Oct 1989

ASJC Scopus subject areas

  • Neuroscience(all)

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