Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats Journal Article


Author(s): Millán, Carmelo; Castro, Enrique G; Torres, Magdalena; Shigemoto, Ryuichi; Sánchez-Prieto, José
Article Title: Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats
Affiliation
Abstract: The modulation of calcium channels by metabotropic glutamate receptors (mGluRs) is a key event in the fine-tuning of neurotransmitter release. Here we report that, in cerebrocortical nerve terminals of adult rats, the inhibition of glutamate release is mediated by mGluR7. In this preparation, the major component of glutamate release is supported by P/Q-type Ca2+ channels (72.7%). However, mGluR7 selectively reduced the release component that is associated with N-type Ca2+ channels (29.9%). Inhibition of P/Q channels by mGluR7 is not masked by the higher efficiency of these channels in driving glutamate release when compared with N-type channels. Thus, activation of mGluR7 failed to reduce the release associated with P/Q channels when the extracellular calcium concentration, ([Ca2+]o), was reduced from 1.3 to 0.5 mM. Through Ca2+ imaging, we show that Ca2+ channels are distributed in a heterogeneous manner in individual nerve terminals. Indeed, in this preparation, nerve terminals were observed that contain N-type (31.1%; conotoxin GVIA-sensitive) or P/Q-type (64.3%; agatoxin IVA-sensitive) channels or that were insensitive to these two toxins (4.6%). Interestingly, the great majority of the responses to L-AP4 (95.4%) were observed in nerve terminals containing N-type channels. This specific co-localization of mGluR7 and N-type Ca2+-channels could explain the failure of the receptor to inhibit the P/Q channel-associated release component and also reveal the existence of specific targeting mechanisms to localize the two proteins in the same nerve terminal subset.
Keywords: Glutamate receptor; unclassified drug; calcium channel N type; calcium channel P type; calcium channel Q type; calcium ion; glutamate receptor 7
Journal Title: Journal of Biological Chemistry
Volume: 278
Issue 26
ISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2003-07-27
Start Page: 23955
End Page: 23962
DOI: 10.1074/jbc.M211471200
Open access: no