Non-additive potentiation of glutamate release by phorbol esters and metabotropic mGlu7 receptor in cerebrocortical nerve terminals

作者：Martin Ricardo; Bartolome Martin David; Torres Magdalena; Sanchez Prieto Jose^*

来源：Journal of Neurochemistry, 2011, 116(4): 476-485.

DOI：10.1111/j.1471-4159.2010.07134.x

• glutamate release potentiation
• mGluR7
• Munc13-1
• Munc13-2
• nerve terminal lacking N-type Ca2+channels
• N-type Ca2+channels
• P
• Q-type Ca2+channels
• phorbol esters

P>We recently showed that prolonged activation of metabotropic glutamate receptor 7 (mGlu7) potentiates glutamate release. This signalling involves phospholipase C activation via a pertussis toxin insensitive G protein and the subsequent hydrolysis of phosphatidylinositol (4,5)-bisphosphate. Release potentiation is independent of protein kinase C activation but it is dependent on the downstream release machinery, as reflected by the concomitant translocation of active zone Munc13-1 protein from the soluble to particulate fractions. Here we show that phorbol ester and mGlu7 receptor-dependent facilitation of neurotransmitter release is not additive, suggesting they share a common signalling mechanism. However, release potentiation is restricted to release sites that express N-type Ca2+ channels, because phorbol ester and mGlu7 receptor-mediated release potentiation are absent in nerve terminals from mice lacking N-type Ca2+ channels. In addition, phorbol esters but not mGlu7 receptors potentiate release at nerve terminals with P/Q-type Ca2+ channels, although only under restricted conditions of Ca2+ influx. The differential effect of phorbol esters at nerve terminals with either N- or P/Q-type Ca2+ channels seems to be unrelated to the type Munc13 isoform expressed, and it is more likely dependent on other properties of the release machinery.

• 出版日期2011-2