title: Potentiation of mGlu7 receptor-mediated glutamate release at nerve terminals containing N and P/Q type Ca2+ channels.
abstract: Calcium channels that mediate glutamate release (N-type and P/Q-type) are expressed in distinct populations of cerebrocortical nerve terminals in adult mice. mGlu7 receptors are exclusively expressed in nerve terminals containing N-type Ca(2+) channels, which are less tightly coupled to glutamate release than P/Q-type Ca(2+) channels. We recently reported that in addition to inhibit, mGlu7 receptors can also potentiate glutamate release via phosphatidyl inositol (4,5)-bisphosphate hydrolysis and activation of the non-kinase diacylglycerol binding protein Munc13-1, a protein that primes synaptic vesicles for exocytosis. Here, we assessed whether mGlu7 receptor-mediated potentiation of glutamate release is restricted to nerve terminals expressing N-type Ca(2+) channels to compensate for their weak coupling to release. In the hippocampus, mGlu7 receptors are expressed both in nerve terminals containing N-type Ca(2+) channels and in nerve terminals containing P/Q-type Ca(2+) channels. When analyzed, we observed potentiation of mGlu7 receptor mediated release in wild type hippocampal nerve terminals at physiological (1.3 mM) and low (0.1 mM) concentrations of external Ca(2+). By contrast, in nerve terminals from mice lacking the α1B subunit of N-type channels (Ca(v)2.2), in which evoked release is mediated by P/Q-type channels only, no release potentiation was observed at 1.3 mM Ca(2+). We conclude that release potentiation at 1.3 mM [Ca(2+)](e) occurs in nerve terminals expressing N-type channels, whereas that which occurs at low 0.1 mM [Ca(2+)](e) represents the release from nerve terminals containing P/Q-type Ca(2+) channels. Although, mGlu7 receptor mediated potentiation is independent of Ca(2+) channel activity, as it was induced by the Ca(2+) ionophore ionomycin, release potentiation is influenced by the Ca(2+) channel type and/or the associated release machinery.
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Ferrero
authors.forename: David
authors.initials: D
authors.lastname: Bartolomé-Martín
authors.forename: Magdalena
authors.initials: M
authors.lastname: Torres
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Prieto
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000502:physiology*; D020865:Calcium Channels, P-Type / Q000502:physiology*; D020907:Calcium Channels, Q-Type / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009411:Nerve Endings / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*
chemical_list: D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D018698:Glutamic Acid