Referenced in: none

Automatically associated channels: BKβ

Title: Role of epoxyeicosatrienoic acids as autocrine metabolites in glutamate-mediated K+ signaling in perivascular astrocytes.

Authors: Haruki Higashimori, Víctor M Blanco, Vengopal Raju Tuniki, John R Falck, Jessica A Filosa

Journal, date & volume: Am. J. Physiol., Cell Physiol., 2010 Nov , 299, C1068-78

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20844244

Abstract
Epoxyeicosatrienoic acids (EETs), synthesized and released by astrocytes in response to glutamate, are known to play a pivotal role in neurovascular coupling. In vascular smooth muscle cells (VSMC), EETs activate large-conductance, Ca(2+)-activated K(+) (BK) channels resulting in hyperpolarization and vasodilation. However, the functional role and mechanism of action for glial-derived EETs are still to be determined. In this study, we evaluated the effect of the synthetic EET analog 11-nonyloxy-undec-8(Z)-enoic acid (NUD-GA) on outward K(+) currents mediated by calcium-activated K(+) channels. Addition of NUD-GA significantly increased intracellular Ca(2+) and outward K(+) currents in perivascular astrocytes. NUD-GA-induced currents were significantly inhibited by BK channel blockers paxilline and tetraethylammonium (TEA) (23.4 ± 2.4%; P < 0.0005). Similarly, NUD-GA-induced currents were also significantly inhibited in the presence of the small-conductance Ca(2+)-activated K(+) channel inhibitor apamin along with a combination of blockers against glutamate receptors (12.8 ± 2.70%; P < 0.05). No changes in outward currents were observed in the presence of the channel blocker for intermediate-conductance K(+) channels TRAM-34. Blockade of the endogenous production of EETs with N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH) significantly blunted (dl)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD)-induced outward K(+) currents (P < 0.05; n = 6). Both NUD-GA and t-ACPD significantly increased BK channel single open probability; the later was blocked following MS-PPOH incubation. Our data supports the idea that EETs are potent K(+) channel modulators in cortical perivascular astrocytes and further suggest that these metabolites may participate in NVC by modulating the levels of K(+) released at the gliovascular space.