Scotti A L, Chatton J Y, Reuter H
Department of Pharmacology, University of Bern, Switzerland.
Philos Trans R Soc Lond B Biol Sci. 1999 Feb 28;354(1381):357-64. doi: 10.1098/rstb.1999.0387.
The release of neurotransmitter from presynaptic terminals depends on an increase in the intracellular Ca2+ concentration ([Ca2+]i). In addition to the opening of presynaptic Ca2+ channels during excitation, other Ca2+ transport systems may be involved in changes in [Ca2+]i. We have studied the regulation of [Ca2+]i in nerve terminals of hippocampal cells in culture by the Na(+)-Ca2+ exchanger and by mitochondria. In addition, we have measured changes in the frequency of spontaneous excitatory postsynaptic currents (sEPSC) before and after the inhibition of the exchanger and of mitochondrial metabolism. We found rather heterogeneous [Ca2+]i responses of individual presynaptic terminals after inhibition of Na(+)-Ca2+ exchange. The increase in [Ca2+]i became more uniform and much larger after additional treatment of the cells with mitochondrial inhibitors. Correspondingly, sEPSC frequencies changed very little when only Na(+)-Ca2+ exchange was inhibited, but increased dramatically after additional inhibition of mitochondria. Our results provide evidence for prominent roles of Na(+)-Ca2+ exchange and mitochondria in presynaptic Ca2+ regulation and spontaneous glutamate release.
神经递质从突触前终末的释放依赖于细胞内钙离子浓度（[Ca2+]i）的升高。除了兴奋时突触前钙离子通道的开放，其他钙离子转运系统可能也参与了[Ca2+]i的变化。我们研究了培养的海马细胞神经终末中Na(+)-Ca2+交换体和线粒体对[Ca2+]i的调节作用。此外，我们还测量了抑制交换体和线粒体代谢前后自发兴奋性突触后电流（sEPSC）频率的变化。我们发现，抑制Na(+)-Ca2+交换后，单个突触前终末的[Ca2+]i反应相当不均一。在用线粒体抑制剂进一步处理细胞后，[Ca2+]i的升高变得更加一致且幅度更大。相应地，仅抑制Na(+)-Ca2+交换时，sEPSC频率变化很小，但在进一步抑制线粒体后显著增加。我们的结果为Na(+)-Ca2+交换体和线粒体在突触前钙离子调节及自发谷氨酸释放中的重要作用提供了证据。
