Modulation of acid sensing ion channel dependent protonergic neurotransmission at the mouse calyx of Held
Modulation of acid sensing ion channel dependent protonergic neurotransmission at the mouse calyx of Held
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DOI：
10.1016/j.neuroscience.2019.04.023
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发表时间：
2020-07-15
期刊：
影响因子：
3.3
通讯作者：
Uchitel, Osvaldo D.
中科院分区：
文献类型：
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作者：
Gonzalez-Inchauspe, Carlota;Natalia Gobetto, Maria;Uchitel, Osvaldo D.
酸敏感离子通道 (ASIC) 调节突触活动并在神经退行性疾病中发挥重要作用。据报道，同源 ASIC-1a 通道在 CNS 听觉系统梯形体内侧核 (MNTB) 的神经元中表达。在突触传递过程中，突触间隙的酸化可能是由于神经递质和 H+ 从突触小泡中共同释放而导致的，从而激活了 3 周龄以下小鼠的突触后 ASIC-1a 通道。这会产生突触电流 (ASIC1a-SC)，并添加到谷氨酸能兴奋性突触后电流 (EPSC) 中。在这里，我们报告说，组胺等神经调节剂以及乳酸和精胺等天然产物以附加形式增强 ASIC1a-SC，使得兴奋性 ASIC 突触电流以及相关的钙流入变得显着大且具有生理相关性。我们证明，内源性神经调节剂增强的 ASIC1a-SC 能够在没有谷氨酸能 EPSC 的情况下支持突触传递。此外，在高频刺激 (HFS) 下，ASIC1a-SC 有助于减少短期抑郁 (STD)，并且它们的贡献在发育的早期阶段更为相关。由于 ASIC 通道存在于几乎所有类型的神经元中，并且突触小泡内容物是酸性的，因此质子参与突触传递及其通过内源性物质的增强可能是整个中枢神经系统的普遍现象。本文是特刊的一部分，题为：纪念里卡多·米莱迪 - 二十世纪至二十一世纪杰出的神经科学家。 (c) 2019 年国际广播组织。
Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. It has been reported that homomeric ASIC-1a channels are expressed in neurons of the medial nucleus of the trapezoid body (MNTB) of the auditory system in the CNS. During synaptic transmission, acidification of the synaptic cleft presumably due to the co -release of neurotransmitter and H+ from synaptic vesicles activates postsynaptic ASIC-1a channels in mice up to 3 weeks old. This generates synaptic currents (ASIC1a-SCs) that add to the glutamatergic excita- tory postsynaptic currents (EPSCs). Here we report that neuromodulators like histamine and natural products like lactate and spermine potentiate ASIC1a-SCs in an additive form such that excitatory ASIC synaptic currents as well as the asso- ciated calcium influx become significantly large and physiologically relevant. We show that ASIC1a-SCs enhanced by endogenous neuromodulators are capable of supporting synaptic transmission in the absence of glutamatergic EPSCs. Furthermore, at high frequency stimulation (HFS), ASIC1a-SCs contribute to diminish short term depression (STD) and their contribution is even more relevant at early stages of development. Since ASIC channels are present in almost all types of neurons and synaptic vesicles content is acid, the participation of protons in synaptic transmission and its potentiation by endogenous substances could be a general phenomenon across the central nervous system. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries . (c) 2019 IBRO.