| Abstract No.: | C-B3070 |
| Country: | Canada |
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| Title: | PANEXIN-1 HEMICHANNELS CONTRIBUTE TO NMDA RECEPTOR DEPENDANT INTERICTAL BURSTING IN THE RAT HIPPOCAMPAL SLICE. |
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| Authors/Affiliations: | 1 Ravi Rungta*; 1 Roger Thompson; 1 Brian MacVicar;
1 University of British Columbia, Vancouver, BC, Canada
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| Content: | Interictal spiking is a persistent bursting (~1 Hz) pattern observed in the hippocampus and may be related to epileptic seizures. The induction of interictal bursts in the rat hippocampal slice involves activation of NMDA receptors, a key component in neuronal excitotoxicity. In recent experiments we have found that NMDA receptor activation in hippocampal neurons (acutely isolated and in brain slices) can lead to a persistent non-selective current due to opening of pannexin hemichannels. We hypothesized that NMDA receptor dependent opening of pannexin-1 hemichannels contributes to the development or maintenance of interictal spiking in the rat hippocampus. Interictal-like bursting was induced by perfusion of 0Mg2+, 5K+ ACSF and monitored in the CA1 and CA3 regions with extracellular field potential recordings. This was inhibited by pre-incubation 50 µM AP-5, a NMDA receptor antagonist. Bursting appeared after AP-5 washout, demonstrating that it was NMDA receptor dependent. Block of pannexin-1 with a short peptide sequence targeted against an extracellular domain of the Panx1 channel (10panx; 100 µM), reduced average peak amplitude (40.9 ± 16.1%) and the number of events (from 2.32 ± 0.49 to 1.51 ± 0.63), of individual bursts. A scramble version of the peptide was ineffective. These data are consistent with the hypothesis that pannexin-1 hemichannels contributes to NMDA dependent interictal bursting, and may therefore represent a novel target for intervention in epilepsy. |
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