Lee Doyun, Lee Kyu-Hee, Ho Won-Kyung, Lee Suk-Ho
National Research Laboratory for Cell Physiology, Department of Physiology, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul 110-799, Korea.
J Neurosci. 2007 Dec 12;27(50):13603-13. doi: 10.1523/JNEUROSCI.3985-07.2007.
Previous studies indicate that boutons from the same axon exhibit distinct Ca2+ dynamics depending on the postsynaptic targets. Mossy fibers of hippocampal granule cells innervate synaptic targets via morphologically distinct boutons. We investigated mitochondrial involvement in the generation of post-tetanic residual Ca2+ (Ca(res)) at large and small en passant mossy fiber boutons (MFBs). Mitochondria limited the [Ca2+]i build-up during high-frequency stimulation (HFS) at large MFBs, but not at small MFBs. The amount of Ca(res), quantified as a time integral of residual [Ca2+]i, was significantly larger at large MFBs than at small MFBs, and that at large MFBs was substantially attenuated by inhibitors of mitochondrial Ca2+ uniporter and mitochondrial Na+/Ca2+ exchanger (mitoNCX). In contrast, blockers of mitoNCX had no effect on the Ca(res) at small MFBs. Post-tetanic Ca(res) has been proposed as a mechanism for post-tetanic potentiation (PTP). We examined mitochondrial involvement in PTP at mossy fiber synapses on hilar mossy cells (MF-->MC synapse) and on hilar interneurons (MF-->HI synapse), which are presumably innervated via large and small MFBs, respectively. Consistent with the differential contribution of mitochondria to Ca(res) at large and small MFBs, mitoNCX blockers significantly reduced the PTP at the MF-->MC synapse, but not at the MF-->HI synapse. In contrast, protein kinase C (PKC) inhibitors significantly reduced the PTP at MF-->HI synapse, but not at the MF-->MC synapse. These results indicate that mitochondria- and PKC-dependent PTP are expressed at distinct hilar mossy fiber synapses depending on postsynaptic targets.
先前的研究表明，来自同一轴突的轴突终扣根据突触后靶点表现出不同的Ca2+动力学。海马颗粒细胞的苔藓纤维通过形态上不同的轴突终扣支配突触靶点。我们研究了线粒体在大小不同的过路苔藓纤维终扣（MFBs）产生强直后残余Ca2+（Ca(res)）过程中的作用。线粒体限制了大MFBs在高频刺激（HFS）期间的[Ca2+]i积累，但对小MFBs没有限制作用。作为残余[Ca2+]i的时间积分量化的Ca(res)量，在大MFBs中比在小MFBs中显著更大，并且大MFBs中的Ca(res)被线粒体Ca2+单向转运体和线粒体Na+/Ca2+交换体（mitoNCX）抑制剂显著减弱。相比之下，mitoNCX阻滞剂对小MFBs中的Ca(res)没有影响。强直后Ca(res)已被提出作为强直后增强（PTP）的一种机制。我们研究了线粒体在苔藓纤维与门区苔藓细胞（MF-->MC突触）和门区中间神经元（MF-->HI突触）突触处PTP中的作用，这两种突触可能分别通过大、小MFBs支配。与线粒体对大、小MFBs中Ca(res)的不同贡献一致，mitoNCX阻滞剂显著降低了MF-->MC突触处的PTP，但对MF-->HI突触处没有影响。相比之下，蛋白激酶C（PKC）抑制剂显著降低了MF-->HI突触处的PTP，但对MF-->MC突触处没有影响。这些结果表明，线粒体依赖性和PKC依赖性PTP根据突触后靶点在不同的门区苔藓纤维突触处表达。
