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PMID:12562994

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Citation

Gee, CE, Benquet, P and Gerber, U (2003) Group I metabotropic glutamate receptors activate a calcium-sensitive transient receptor potential-like conductance in rat hippocampus. J. Physiol. (Lond.) 546:655-64

Abstract

In CA3 pyramidal neurons from organotypic slice cultures, activation of G(q)-coupled group I metabotropic glutamate receptors (mGluRs) induces a non-selective cationic conductance that enhances excitability. We have found that this response shares several properties with conductances that are mediated by the transient receptor potential (TRP) family of ion channels, including inhibition by La(3+), 2-aminoethoxydiphenylborane (2APB), cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12,330A) and a doubly rectifying current-voltage relationship. Stimulation of mGluR1 and mGluR5 converged to activate the TRP-like conductance in a synergistic manner, and activation of either subtype alone produced only a fraction of the normal response. Activation of the cationic current required elevated intracellular Ca(2+). Chelating intracellular Ca(2+) or blocking Ca(2+) entry through voltage-gated Ca(2+) channels attenuated responses to the activation of mGluRs. Conversely, raising intracellular Ca(2+) potentiated mGluR activation of the TRP-like conductance. Under control conditions, blocking G protein activation using intracellular GDPbetaS with or without N-(2, 6-dimethylphenylcarbamoylmethyl) triethylammonium chloride (QX-314) prevented mGluR-mediated activation of the TRP-like conductance. Following G protein blockade, however, the coupling between mGluRs 1 and/or 5 and the TRP-like conductance was rescued by increasing intracellular Ca(2+). This suggests that a G protein-independent signalling pathway is also activated by group I mGluRs. Such a pathway may represent an alternative transduction mechanism to maintain metabotropic responses under conditions where G proteins are functionally uncoupled from their cognate receptors.

Links

PubMed PMC2342598

Keywords

Animals; Calcium/metabolism; Electric Conductivity; GTP-Binding Proteins/physiology; Hippocampus/cytology; Hippocampus/metabolism; Intracellular Membranes/metabolism; Pyramidal Cells/metabolism; Rats; Rats, Wistar; Receptors, Calcium-Sensing; Receptors, Cell Surface/physiology; Receptors, Metabotropic Glutamate/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:GRM1

part_of

GO:0005887: integral component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete


See also

References

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