Subtype-specific expression of group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals.
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 Ca(2+) channel activity. By imaging Ca(2+) in preparations of cerebrocortical nerve terminals, we show that voltage-dependent Ca(2+) 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%) Ca(2+) 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 Ca(2+) 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 Ca(2+) channels, whereas mGluR7 was predominantly (69.9%) located in N-type Ca(2+) channel-expressing terminals. This specific coexpression of different group III mGluRs and Ca(2+) channels may endow synaptic terminals with distinct release properties and reveals the existence of a high degree of presynaptic heterogeneity.
Millán
Carmelo
C
Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain.
Luján
Rafael
R
Shigemoto
Ryuichi
R
Sánchez-Prieto
José
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000378:metabolism; D011189:Potassium Chloride / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; C111435:metabotropic glutamate receptor 8; D018698:Glutamic Acid; D011189:Potassium Chloride; D002118:Calcium; C108823:metabotropic glutamate receptor 4