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The Journal of Neuroscience, December 1, 2000, 20(23):8628-8636
Role of Ca2+ Stores in Metabotropic L-Glutamate Receptor-Mediated Supralinear Ca2+ Signaling in Rat Hippocampal Neurons
Mark G. Rae1, Duncan J. Martin1, Graham L. Collingridge2, and Andrew J. Irving1 1 Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, United Kingdom, and 2 Department of Anatomy, The School of Medical Sciences, University of Bristol, Bristol BS8 1TD, England, United Kingdom
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.
Key words: mGlu; NMDA; Ca2+ stores; Ca2+ release; recency detector; supralinear
Copyright © 2000 Society for Neuroscience 0270-6474/00/20238628-09$05.00/0
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