Subtype-specific expression of Group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals Journal Article


Author(s): Millán, Carmelo; Luján, Rafael; Shigemoto, Ryuichi; Sánchez-Prieto, José
Article Title: Subtype-specific expression of Group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals
Affiliation
Abstract: The release properties of glutamatergic nerve terminals are influenced by a number of factors, including the subtype of voltage-dependent calcium channel and the presence of presynaptic autoreceptors. Group III metabotropic glutamate receptors (mGluRs) mediate feedback inhibition of glutamate release by inhibiting Ca2+ channel activity. By imaging Ca2+ in preparations of cerebrocortical nerve terminals, we show that voltage-dependent Ca2+ channels are distributed in a heterogeneous manner in individual nerve terminals. Presynaptic terminals contained only N-type (47.5%; conotoxin GVIA-sensitive), P/Q-type (3.9%; agatoxin IVA-sensitive), or both N- and P/Q-type (42.6%) Ca2+ channels, although the remainder of the terminals (6.1%) were insensitive to these two toxins. In this preparation, two mGluRs with high and low affinity for L(+)-2-amino-4-phosphonobutyrate were identified by immunocytochemistry as mGluR4 and mGluR7, respectively. These receptors were responsible for 22.2 and 24.1% reduction of glutamate release, and they reduced the Ca2+ response in 24.4 and 30.3% of the nerve terminals, respectively. Interestingly, mGluR4 was largely (73.7%) located in nerve terminals expressing both N- and P/Q-type Ca2+ channels, whereas mGluR7 was predominantly (69.9%) located in N-type Ca2+ channel-expressing terminals. This specific coexpression of different group III mGluRs and Ca2+ channels may endow synaptic terminals with distinct release properties and reveals the existence of a high degree of presynaptic heterogeneity.
Keywords: Glutamate receptor; metabotropic receptor; calcium channel
Journal Title: Journal of Biological Chemistry
Volume: 277
Issue 49
ISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2002-12-02
Start Page: 47796
End Page: 47803
DOI: 10.1074/jbc.M207531200
Open access: no