Anoxia-Induced NMDA Receptor Activation Opens Pannexin Channels via Src Family Kinases

• DOI: 10.1523/jneurosci.1267-12.2012
• Publication Date: 2012-09-05T16:38:31Z
• Authors: Nicholas L. Weili...; Peter L. Tang; Roger J. Thompson
• Keywords: Pannexin; Src family kinase

Anoxic depolarization of pyramidal neurons results from a large inward current that is activated, in part, by excessive glutamate release during exposure to anoxia/ischemia. Pannexin-1 (Panx1) channels can be activated both ischemia and NMDA receptors (NMDARs), but the mechanisms Panx1 activation are unknown. We used whole-cell recordings show pharmacological inhibition or conditional genetic deletion strongly attenuates anoxic CA1 acute brain slices rats mice. Anoxia exogenous Src family kinases (SFKs), as measured increased phosphorylation SFKs at Y416. The SFK inhibitor PP2 prevented opening anoxia. A newly developed interfering peptide targets consensus-like sequence (Y308) attenuated (AD) without affecting activation. Importantly, NMDAR antagonists, d -APV R-CPP, AD currents carried Panx1, combined application 10 panx (a blocker) inhibited same extent either blocker alone. conclude NMDARs anoxia/ischemia recruits open leading sustained neuronal depolarizations.