Trends in Neurosciences
Volume 23, Issue 2, 1 February 2000, Pages 80-88
Journal home page for Trends in Neurosciences

Review
Complex interactions between mGluRs, intracellular Ca2+ stores and ion channels in neurons

https://doi.org/10.1016/S0166-2236(99)01492-7Get rights and content

Abstract

Metabotropic glutamate receptors (mGluRs) can increase intracellular Ca2+ concentration via Ins(1,4,5)P3- and ryanodine-sensitive Ca2+ stores in neurons. Both types of store are coupled functionally to Ca2+-permeable channels found in the plasma membrane. The mGluR-mediated increase in intracellular Ca2+ concentration can activate Ca2+-sensitive K+ channels and Ca2+-dependent nonselective cationic channels. These mGluR-mediated effects often result from mobilization of Ca2+ from ryanodine-sensitive, rather than Ins(1,4,5)P3-sensitive, Ca2+ stores, suggesting that close functional interactions exist between mGluRs, intracellular Ca2+ stores and Ca2+-sensitive ion channels in the membrane.

Section snippets

Neuronal distribution of mGluRs and intracellular Ca2+ pools

The group-I mGluRs display distinct distributions in the CNS. For example, the cerebellum, and in particular the cerebellar Purkinje cells, displays much-stronger mglu1a-receptor immunoreactivity than most other regions of the brain14. In the hippocampus, mglu1a-receptor immunostaining has been found to be strong in interneurons of the CA1 region and in some CA3 pyramidal cells, weaker in granule cells and absent in CA1 pyramidal cells14, 15, 16. However, the hippocampal CA1 pyramidal cells

Functional interactions between mGluRs, RyRs and L-type Ca2+ channels

In addition to activating intracellular Ca2+ stores through Ins(1,4,5)P3 synthesis, group-I mGluRs can also activate RyRs independently of Ins(1,4,5)P3-mediated Ca2+ mobilization. In cerebellar granule cells, mglu1-receptor stimulation triggers Ca2+ entry through L-type Ca2+ channels in a ryanodine-dependent manner via a pertussis-toxin-insentive G protein33 (Fig. 1a). This effect is observed after blocking Ins(1,4,5)P3Rs with heparin, or in the presence of a high intracellular concentration of

Activation of Ca2+-sensitive K+ channels and nonselective cationic channels by mGluRs

In neurons, Ca2+-sensitive K+ channels seem to be located in the proximity of Ca2+ channels52, 53, 54, 55, 56, 57 and sense the intracellular Ca2+ increase induced by group-I mGluR agonists at the submembrane level7, 34, 58, 59. Interestingly, in cerebellar granule cells the mglu1-receptor-mediated activation of Ca2+-dependent K+ channels is blocked completely by ryanodine and nifedipine, indicating that it involves both RyRs and L-type Ca2+ channels34. Moreover, in the same preparation a

Functional consequences of the interaction between mGluRs and RyRs

Are these interactions involved in the refilling of Ca2+ stores? Ca2+ entry through voltage-gated Ca2+ channels might participate in the refilling of Ca2+ stores in hippocampal pyramidal cells5, 28. In rat neocortical pyramidal neurons, the decay timecourse of dendritic Ca2+ transients is prolonged by blockers of Ca2+-ATPase in the endoplasmic reticulum (cyclothiazide and thapsigargin), suggesting an uptake of Ca2+ into Ca2+ stores in the endoplasmic reticulum and clearance of dendritic Ca2+ (

Concluding remarks

Group-I mGluRs are not only coupled to Ins(1,4,5)P3-sensitive Ca2+ stores but also to ryanodine-sensitive Ca2+ stores. Activation of Ins(1,4,5)P3Rs and RyRs can induce an initial small release of Ca2+ from Ins(1,4,5)P3-sensitive Ca2+ stores that triggers further release of Ca2+ from ryanodine-sensitive Ca2+ stores, via a Ca2+-induced Ca2+ release. However, there is evidence to indicate that the mglu1 receptor is also coupled functionally to RyRs in cerebellar granule cells. This coupling is

Acknowledgements

The authors’ research is supported by grants from CEE BIOMED, CEE BIOTECH, Synthelabo, DRET, AFM and Bayer. The authors thank J.P. Pin and L. Vitkovic for critically reading the manuscript, and M. Passama for the figures.

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