Role of Ca2+ stores in metabotropic L-glutamate receptor-mediated supralinear Ca2+ signaling in rat hippocampal neurons

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Rae, Mark G.
Martin, Duncan J.
Collingridge, Graham L.
Irving, Andrew J.
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The role of metabotropic l-glutamate (mGlu) receptors in supralinear Ca2+ signaling was investigated in cultured hippocampal cells using Ca2+ imaging techniques and whole-cell voltage-clamp recording. In neurons, but not glia, global supralinear Ca2+ release from intracellular stores was observed when the mGlu receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) was combined with elevated extracellular K+ levels (10.8 mm), moderate depolarization (15–30 mV), or NMDA (3 μm). There was a delay (2–8 min) before the stores were fully charged, and the enhancement persisted for a short period (up to 10 min) after removal of the store-loading stimulus. Studies with the mGlu receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine demonstrated that these effects were mediated by activation of the mGlu5 receptor subtype. The L-type voltage-gated Ca2+ channel antagonist nifedipine (10 μm) substantially reduced responses to DHPG obtained in the presence of elevated extracellular K+ but not NMDA. This suggests that the Ca2+ that is required to load the stores can enter either through L-type voltage-gated Ca2+ channels or directly through NMDA receptors. The findings that both depolarization and NMDA receptor activation can facilitate mGlu receptor Ca2+ signaling adds considerable flexibility to the processes that underlie activity-dependent changes in synaptic strength. In particular, a temporal separation between the store-loading stimulus and the activation of mGlu receptors could be used as a recency detector in neurons.
mGlu , NMDA , Ca2+ stores , Ca2+ release , Recency detector , Supralinear
Rae, M.G., Martin, D.J., Collingridge, G.L. and Irving, A.J. (2000) ‘Role of ca 2+ stores in metabotropicl-glutamate receptor-mediated supralinear ca 2+ signaling in rat hippocampal neurons’, The Journal of Neuroscience, 20(23), pp. 8628–8636.