Complex interplay between glutamate receptors and intracellular Ca2+ stores during ischaemia in rat spinal cord white matter.
Electrophysiological recordings of propagated compound action potentials (CAPs) and axonal Ca(2+) measurements using confocal microscopy were used to study the interplay between AMPA receptors and intracellullar Ca(2+) stores in rat spinal dorsal columns subjected to in vitro combined oxygen and glucose deprivation (OGD). Removal of Ca(2+) 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 0Ca(2+) + EGTA perfusate was ineffective. Similarly, blocking ryanodine receptor-mediated Ca(2+) mobilization from internal stores (0Ca(2+) + nimodipine or 0Ca(2+) + ryanodine), or inositol 1,4,5-trisphosphate (IP(3))-dependent Ca(2+) release (block of group 1 metabotropic glutamate receptors with 1-aminoindan-1,5-dicarboxylic acid, inhibition of phospholipase C with U73122 or IP(3) receptor block with 2APB; each in 0Ca(2+)) 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 Ca(2+) 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 Ca(2+) mobilization from intracellular Ca(2+) stores. We propose that AMPA receptors may not only allow Ca(2+) influx from the extracellular space, but may also significantly influence Ca(2+) release from intra-axonal Ca(2+) 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.
Ouardouz
Mohamed
M
Division of Neuroscience, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9.
Malek
Sameh
S
Coderre
Elaine
E
Stys
Peter K
PK
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000378:metabolism*; D013116:Spinal Cord / Q000098:blood supply* / Q000378:metabolism*; D020760:Spinal Cord Ischemia / Q000378:metabolism*
D018091:Receptors, AMPA; D002118:Calcium