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

J Biol Chem. 2002 Dec 6;277(49):47796-803. doi: 10.1074/jbc.M207531200. Epub 2002 Oct 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Calcium Channels, N-Type / metabolism
  • Calcium Channels, P-Type / metabolism
  • Calcium Channels, Q-Type / metabolism
  • Dose-Response Relationship, Drug
  • Glutamic Acid / metabolism
  • Immunohistochemistry
  • Kinetics
  • Male
  • Neurons / metabolism
  • Potassium Chloride / metabolism
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / chemistry*
  • Receptors, Metabotropic Glutamate / metabolism
  • Synaptosomes / metabolism
  • Time Factors


  • Calcium Channels
  • Calcium Channels, N-Type
  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 7
  • metabotropic glutamate receptor 8
  • Glutamic Acid
  • Potassium Chloride
  • Calcium
  • metabotropic glutamate receptor 4