Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain.
Neuropharmacology. 2013 Apr;67:213-22. doi: 10.1016/j.neuropharm.2012.10.032. Epub 2012 Nov 19.
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+) occurs in nerve terminals expressing N-type channels, whereas that which occurs at low 0.1 mM Ca(2+) 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.
钙通道介导谷氨酸释放（N 型和 P/Q 型）在成年小鼠大脑皮质神经末梢的不同群体中表达。mGlu7 受体仅表达在含有 N 型 Ca2+通道的神经末梢中，与 P/Q 型 Ca2+通道相比，N 型 Ca2+通道与谷氨酸释放的耦合程度较弱。我们最近报道，除了抑制作用外，mGlu7 受体还可以通过磷脂酰肌醇（4,5）-双磷酸水解和非激酶二酰基甘油结合蛋白 Munc13-1 的激活来增强谷氨酸释放，Munc13-1 是一种使突触囊泡为胞吐作用做好准备的蛋白质。在这里，我们评估了 mGlu7 受体介导的谷氨酸释放增强是否仅限于表达 N 型 Ca2+通道的神经末梢，以补偿其与释放的弱耦合。在海马体中，mGlu7 受体既表达在含有 N 型 Ca2+通道的神经末梢中，也表达在含有 P/Q 型 Ca2+通道的神经末梢中。当进行分析时，我们观察到在生理（1.3 mM）和低（0.1 mM）外部 Ca2+浓度下，野生型海马神经末梢中 mGlu7 受体介导的释放增强。相比之下，在缺乏 N 型通道的α1B 亚基（Ca(v)2.2）的小鼠神经末梢中，仅由 P/Q 型通道介导诱发释放，在 1.3 mM Ca2+下未观察到释放增强。我们得出结论，在表达 N 型通道的神经末梢中，在 1.3 mM [Ca2+]（e）下发生释放增强，而在低 0.1 mM [Ca2+]（e）下发生的释放增强代表来自含有 P/Q 型 Ca2+通道的神经末梢的释放。尽管 mGlu7 受体介导的增强与 Ca2+通道活性无关，因为它是由 Ca2+离子载体离子霉素诱导的，但释放增强受 Ca2+通道类型和/或相关释放机制的影响。
