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Pannexin channels and ischaemia
Author(s) -
Thompson Roger J.
Publication year - 2014
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.282426
Subject(s) - pannexin , excitotoxicity , glutamate receptor , nmda receptor , neuroscience , proto oncogene tyrosine protein kinase src , hippocampal formation , kinase , allosteric regulation , microbiology and biotechnology , phosphorylation , ion channel , ischemia , chemistry , biology , biophysics , receptor , biochemistry , medicine , intracellular , connexin , gap junction
An ischaemic stroke occurs during loss of blood flow in the brain from the occlusion of a blood vessel. The ischaemia itself comprises a complex array of insults, including oxygen and glucose deprivation (OGD), glutamate excitotoxicity, acidification/hypercapnia, and loss of sheer forces. A substantial amount of knowledge has accumulated that define the excitotoxic cascade downstream of N ‐methyl‐ d ‐aspartate receptors (NMDARs). While the NMDAR can influence numerous downstream elements, one critical target during ischaemia is the ion channel, pannexin‐1 (Panx1). The C‐terminal region of Panx1 appears critical for its regulation under a host of physiological and pathological stimuli. We have shown using hippocampal brain slices that Panx1 is activated by NMDARs through Src family kinases. However, it is not yet certain if this involves direct phosphorylation of Panx1 or an allosteric interaction between the channel's C‐terminal tail and Src. Interestingly, Panx1 opening during ischaemia and NMDAR over‐activation is antagonized by an interfering peptide that comprises amino acids 305–318 of Panx1. Thus, targeting the activation of Panx1 by NMDARs and Src kinases is an attractive mechanism to reduce anoxic depolarizations and neuronal death.