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This Article Full Text Full Text (PDF) All Versions of this Article: 577/1/191    most recent jphysiol.2006.116798v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ouardouz, M. Articles by Stys, P. K. Search for Related Content PubMed PubMed Citation Articles by Ouardouz, M. Articles by Stys, P. K. Related Collections Neuroscience

¹ Division of Neuroscience, Ottawa Health Research Institute, University of Ottawa, Canada K1Y 4E9

Electrophysiological recordings of propagated compound action potentials (CAPs) and axonal Ca²⁺ measurements using confocal microscopy were used to study the interplay between AMPA receptors and intracellullar Ca²⁺ stores in rat spinal dorsal columns subjected to in vitro combined oxygen and glucose deprivation (OGD). Removal of Ca²⁺ or Na⁺ from the perfusate was protective after 30 but not 60 min of OGD. TTX was ineffective with either exposure, consistent with its modest effect on ischaemic depolarization. In contrast, AMPA antagonists were very protective, even after 60 min of OGD where 0Ca²⁺ + EGTA perfusate was ineffective. Similarly, blocking ryanodine receptor-mediated Ca²⁺ mobilization from internal stores (0Ca²⁺ + nimodipine or 0Ca²⁺ + ryanodine), or inositol 1,4,5-trisphosphate (IP₃)-dependent Ca²⁺ release (block of group 1 metabotropic glutamate receptors with 1-aminoindan-1,5-dicarboxylic acid, inhibition of phospholipase C with U73122 or IP₃ receptor block with 2APB; each in 0Ca²⁺) were each very protective, with the combination resulting in virtually complete functional recovery after 1 h OGD (97 ± 32% CAP recovery versus 4 ± 6% in artificial cerebrospinal fluid). AMPA induced a rise in Ca²⁺ concentration in normoxic axons, which was greatly reduced by blocking ryanodine receptors. Our data therefore suggest a novel and surprisingly complex interplay between AMPA receptors and Ca²⁺ mobilization from intracellular Ca²⁺ stores. We propose that AMPA receptors may not only allow Ca²⁺ influx from the extracellular space, but may also significantly influence Ca²⁺ release from intra-axonal Ca²⁺ stores. In dorsal column axons, AMPA receptor-dependent mechanisms appear to exert a greater influence than voltage-gated Na⁺ channels on functional outcome following OGD.

(Received 7 July 2006; accepted after revision 29 August 2006; first published online 31 August 2006)
Corresponding author P. K. Stys: Division of Neuroscience, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9. Email: pstys{at}ohri.ca