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 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.
Highlights
The release properties of presynaptic terminals are determined by factors such as the presence of auto- or heteroreceptors, the subtype of voltage-dependent Ca2ϩ channel coupled to neurotransmitter release at the active zone, and the machinery of synaptic vesicle fusion
This release was reduced by 22.2 Ϯ 1.4% (n ϭ 8) by the group III metabotropic glutamate receptors (mGluRs) agonist L-AP4 at 20 M and by 46.3 Ϯ 1.3% (n ϭ 8) when the agonist concentration was increased to 1 mM (Fig. 1A)
Because group III mGluR-mediated inhibition of induced glutamate release is the consequence of a reduction in Ca2ϩ channel activity [8, 10, 17, 19], Ca2ϩ imaging experiments were performed to determine which subpopulation of nerve terminals expresses these receptors
Summary
The release properties of presynaptic terminals are determined by factors such as the presence of auto- or heteroreceptors, the subtype of voltage-dependent Ca2ϩ channel coupled to neurotransmitter release at the active zone, and the machinery of synaptic vesicle fusion. A number of electrophysiological studies have shown that the release of glutamate depends primarily on the activity of P/Q- and N-type Ca2ϩ channels [21,22,23,24,25] These same electrophysiological studies have suggested that Ca2ϩ channels exhibit a heterogeneous distribution in glutamatergic nerve terminals, which may express N- or P/Q-type calcium channels or a combination of both. Because the Ca2ϩ channel profile may confer specific release properties to glutamatergic nerve terminals, it is possible that the distinct group III mGluRs are restricted to subpopulations of nerve terminals depending upon the type or combination of Ca2ϩ channels present. This paper is available on line at http://www.jbc.org mGluRs and Ca2ϩ Channels in Single Nerve Terminals
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