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J. Biol. Chem. 277 (49): 47796-47803

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Subtype-specific Expression of Group III Metabotropic Glutamate Receptors and Ca2+ Channels in Single Nerve Terminals*

Carmelo MillánDagger , Rafael Luján§, Ryuichi Shigemoto, and José Sánchez-PrietoDagger ||

From the Dagger  Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain, the § Centro Regional de Investigaciones Biomédicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Campus de Albacete, 02071 Albacete, Spain, and the  National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan

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.

* This work was supported by Ministerio de Ciencia y Tecnologia Grant BFI2001-1436 and Dirección General de Investigación de la Comunidad de Madrid Grant 08.5/0075.1/2000 (to J. S.-P.) and European Community Grant QLG3-CT-1999-00192 (to R. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| To whom correspondence should be addressed. Tel.: 34-91-394-3891; Fax: 34-91-394-3909; E-mail:

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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