An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons

Yoshinori Hayashi, Saori Morinaga, Xia Liu, Jing Zhang, Zhou Wu, Takeshi Yokoyama, Hiroshi Nakanishi

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Abstract

Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca2+-activated K+ (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (I NMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated I NMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on I NMDA-OUT. A direct perfusion of 3,5'-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated I NMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of I NMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons.

Original languageEnglish
Article number5079597
JournalMediators of Inflammation
Volume2016
DOIs
Publication statusPublished - Jan 1 2016

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Large-Conductance Calcium-Activated Potassium Channels
N-Methylaspartate
Neurons
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
N-Methyl-D-Aspartate Receptors
Dinoprostone
Receptors, Prostaglandin E, EP1 Subtype
Calcium-Activated Potassium Channels
Prostaglandin-Endoperoxide Synthases
Cyclic AMP
Prostaglandins
Perfusion

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cell Biology

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An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons. / Hayashi, Yoshinori; Morinaga, Saori; Liu, Xia; Zhang, Jing; Wu, Zhou; Yokoyama, Takeshi; Nakanishi, Hiroshi.

In: Mediators of Inflammation, Vol. 2016, 5079597, 01.01.2016.

Research output: Contribution to journalArticle

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