Presynaptic release probability is increased in hippocampal neurons from ASIC1 knockout mice
Presynaptic release probability is increased in hippocampal neurons from ASIC1 knockout mice
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DOI：
10.1152/jn.00940.2007
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发表时间：
2008-02-01
影响因子：
2.5
通讯作者：
Askwith, Candice C.
中科院分区：
文献类型：
--
作者：
Cho, Jun-Hyeong;Askwith, Candice C.
酸敏感离子通道（ASIC）是H+门控通道，其响应于细胞外酸而产生瞬时阳离子电流。ASIC在整个大脑的神经元中表达，ASIC 1敲除小鼠在学习和记忆方面表现出行为障碍。然而，ASIC在突触传递中的作用还没有完全了解。我们使用野生型和ASIC基因敲除小鼠海马神经元的微岛培养物分析了ASIC参与突触传递的情况。野生型和ASIC基因敲除神经元之间的单个动作电位（AP）诱发的兴奋性突触后电流（EPSC）没有显著差异。然而，与野生型神经元相比，ASIC 1基因敲除神经元的成对脉冲比（PPRs）降低，自发性微型EPSC（mEPSC）以更高的频率发生。开放通道阻滞剂MK-801对NMDA受体的渐进阻滞在ASIC 1敲除神经元中也更快。mEPSC的振幅和衰减时间常数，以及大小和重新填充的容易释放的池，在ASIC 1敲除和野生型神经元相似。最后，释放概率，这是估计直接作为AP诱发的高渗蔗糖诱导的电荷转移的比率，增加ASIC 1基因敲除神经元。ASIC 1a转染到ASIC 1敲除的神经元中增加了PPR，这表明释放概率的改变不是ASIC 1敲除小鼠内发育补偿的结果。总之，这些发现表明，来自ASIC 1敲除小鼠的神经元释放神经递质的可能性增加，并表明ASIC 1a可以影响突触传递的突触前机制。
Acid-sensing ion channels (ASICs) are H+-gated channels that produce transient cation currents in response to extracellular acid. ASICs are expressed in neurons throughout the brain, and ASIC1 knockout mice show behavioral impairments in learning and memory. The role of ASICs in synaptic transmission, however, is not thoroughly understood. We analyzed the involvement of ASICs in synaptic transmission using microisland cultures of hippocampal neurons from wild-type and ASIC knockout mice. There was no significant difference in single action potential (AP)-evoked excitatory postsynaptic currents (EPSCs) between wild-type and ASIC knockout neurons. However, paired-pulse ratios (PPRs) were reduced and spontaneous miniature EPSCs (mEPSCs) occurred at a higher frequency in ASIC1 knockout neurons compared with wildtype neurons. The progressive block of NMDA receptors by an open channel blocker, MK-801, was also faster in ASIC1 knockout neurons. The amplitude and decay time constant of mEPSCs, as well as the size and refilling of the readily releasable pool, were similar in ASIC1 knockout and wild-type neurons. Finally, the release probability, which was estimated directly as the ratio of AP-evoked to hypertonic sucrose-induced charge transfer, was increased in ASIC1 knockout neurons. Transfection of ASIC1a into ASIC1 knockout neurons increased the PPRs, suggesting that alterations in release probability were not the result of developmental compensation within the ASIC1 knockout mice. Together, these findings demonstrate that neurons from ASIC1 knockout mice have an increased probability of neurotransmitter release and indicate that ASIC1a can affect presynaptic mechanisms of synaptic transmission.