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 Ca2+ channels, which are less tightly coupled to glutamate release than P/Q-type Ca2+ 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 Ca2+ channels to compensate for their weak coupling to release. In the hippocampus, mGlu7 receptors are expressed both in nerve terminals containing N-type Ca2+ channels and in nerve terminals containing P/Q-type Ca2+ 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 Ca2+. By contrast, in nerve terminals from mice lacking the α1B subunit of N-type channels (Cav2.2), in which evoked release is mediated by P/Q-type channels only, no release potentiation was observed at 1.3 mM Ca2+. We conclude that release potentiation at 1.3 mM [Ca2+]e occurs in nerve terminals expressing N-type channels, whereas that which occurs at low 0.1 mM [Ca2+]e represents the release from nerve terminals containing P/Q-type Ca2+ channels. Although, mGlu7 receptor mediated potentiation is independent of Ca2+ channel activity, as it was induced by the Ca2+ ionophore ionomycin, release potentiation is influenced by the Ca2+ channel type and/or the associated release machinery.