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RGS7 Protein Suppression of Gao Protein‐Mediated α2A‐Adrenergic Receptor Inhibition of Mouse Hippocampal CA3 Epileptiform Activity
Author(s) -
Nelson Brian William,
Goldenstein Brianna,
Xu Ke,
Luger Elizabeth,
Wald Jenna,
O'shea Lorraine,
Weinshenker David,
Sjogren Benita,
Charbeneau Raelene,
Huang Xinyan,
Neubig Richard,
Doze Van
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.587.3
Subject(s) - hippocampal formation , g protein , receptor , inhibitory postsynaptic potential , genetically modified mouse , knockout mouse , chemistry , hippocampus , epilepsy , medicine , endocrinology , pharmacology , biology , microbiology and biotechnology , neuroscience , transgene , biochemistry , gene
G‐protein coupled α 2 adrenergic receptor (AR) activation by epinephrine (EPI) inhibits epileptiform activity in the mouse hippocampal CA3 region. The mechanism underlying this action is unclear. This study investigated which subtypes of α 2 ARs, G‐proteins (Gα o or Gα i ), and RGS proteins were involved in this response using recordings of hippocampal CA3 epileptiform bursts in mouse brain slices. First, we determined that this effect was mediated by the α 2A AR subtype as the inhibitory action of EPI on epileptiform burst frequency was abolished in slices from α 2A AR, but not α 2C AR, knockout mice. Next, using transgenic mice with the G184S Gnai2 allele (knock‐ins) which interrupts G‐protein α unit binding to regulators of G‐protein signaling (RGS), we found that the α 2A AR antiepileptic effects of EPI were enhanced in hippocampal slices from mutant Gα o mice but not Gα i2 mice. Finally, hypomorph mice with very low RGS7 protein levels were found to have increased α 2A AR‐mediated hippocampal antiepileptic actions compared to their littermate controls. These results indicate that the EPI‐mediated inhibition of mouse hippocampal CA3 epileptiform burst activity is through an α 2A AR/Gα o ‐mediated pathway under strong inhibitory control by proteins of the RGS7 family. This suggests a possible role for selective α 2A AR agonists or RGS7 inhibitors as a novel antiepileptic drug therapy.