Format

Send to

Choose Destination
See comment in PubMed Commons below
J Neurochem. 2010 Jul;114(1):28-38. doi: 10.1111/j.1471-4159.2010.06602.x. Epub 2010 Jan 20.

Na+/K+-ATPase inhibitor palytoxin enhances vulnerability of cultured cerebellar neurons to domoic acid via sodium-dependent mechanisms.

Author information

  • 1Departament of Biochemistry and Molecular Biology, Institute of Biotechnlogy of Asturias, University of Oviedo, 33006 Oviedo, Spain.

Abstract

Dysfunction or deficiency of the Na(+)/K(+)-ATPase appears to be a common event in a variety of pathological conditions in the central nervous system. Studies on neurotoxicity associated to impaired Na(+)/K(+)-ATPase activity have focused on NMDA receptors, while the involvement of non-NMDA receptors has been much less explored. We show that mild, non-toxic, exposures to the Na(+)/K(+)-ATPase inhibitor palytoxin (PTX) synergistically sensitized the vulnerability of neurons to normally non-toxic concentrations of domoic acid, leaving NMDA receptor-mediated excitotoxic response unaltered. Enhancement of excitotoxicity required at least 1 h pre-exposure to PTX, was not observed after longer exposures to PTX, and did not require RNA synthesis. PTX caused a voltage-sensitive Na(+) channel-independent increase in intracellular Na(+). Both intracellular Na(+) increase and potentiation of excitotoxicity depended upon the external concentrations of Na(+) and Cl(-), and were suppressed by the anion exchanger blocker 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid in a dose-dependent manner. Other stilbene derivatives, chloride channel antagonists or Na(+) cotransporter inhibitors proved ineffective. Our results demonstrate a crucial role for Na(+)/K(+)-ATPase activity in determining neuronal vulnerability to domoic acid-mediated excitotoxicity. They also raise reasonable concern about possible risks for human health associated to the ingestion of low amounts of phycotoxins PTX and domoic acid in food.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Write to the Help Desk