5-HT3R-sourced calcium enhances glutamate release from a distinct vesicle pool.
5-HT3R-sourced calcium enhances glutamate release from a distinct vesicle pool.
复制标题
5-HT3R 来源的钙可增强独特囊泡池中谷氨酸的释放。
DOI：
10.1016/j.brainres.2019.146346
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Andresen,MichaelC
中科院分区：
文献类型：
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作者：
Fawley,JessicaA;Doyle,MarkW;Andresen,MichaelC
5-羟色胺3受体（5-HT 3R）是在孤束（ST）传入中不均匀表达的钙渗透通道。ST传入神经在孤束核（NTS）中形成突触，并依赖于电压依赖性钙通道（CaV）的混合来控制同步谷氨酸释放（ST-EPSC）。CaV激活触发额外的，延迟释放的谷氨酸（异步EPSC）后，ST-EPSC，但仅从传入表达钙渗透性，瞬时受体电位香草素1型受体（TRPV 1）。大多数传入神经表达TRPV 1，并具有独立于CaV的高自发谷氨酸释放率（sEPSC）。在这里，我们测试了5-HT 3R来源的钙是否有助于大鼠水平NTS切片中这些不同形式的谷氨酸盐释放。5-HT 3R选择性激动剂，间氯苯双胍盐酸盐（PBG），增强sEPSC和/或延迟ST-EPSC的到达时间（即增加的潜伏期）。特异性5-HT 3R拮抗剂昂丹司琼减弱了与5-HT 3R直接激活一致的这些作用。PBG不改变ST-EPSC振幅或异步EPSC。这些独立的行动表明两个不同的5-HT 3R的位置，轴突表达，阻碍传导和终端的表达，动员一个自发的囊泡池。EGTA-AM与钙螯合使5-HT 3R激活的sEPSC的频率减少一半。螯合敏感性和抗性sEPSC的混合物表明5-HT 3R活化的囊泡跨越通道的远端（微域）和近端（纳米域）的钙扩散距离。我们的研究结果表明，5-HT 3Rs的钙结构域不重叠其他钙源或其各自的囊泡池。5-HT 3R作为多个独立的突触信号传导机制的一部分，在ST传入上添加了独特的钙源。
The serotonin 3 receptor (5-HT3R) is a calcium-permeant channel heterogeneously expressed in solitary tract (ST) afferents. ST afferents synapse in the nucleus of the solitary tract (NTS) and rely on a mix of voltage-dependent calcium channels (CaVs) to control synchronous glutamate release (ST-EPSCs). CaV activation triggers additional, delayed release of glutamate (asynchronous EPSCs) that trails after the ST-EPSCs but only from afferents expressing the calcium-permeable, transient receptor potential vanilloid type 1 receptor (TRPV1). Most afferents express TRPV1 and have high rates of spontaneous glutamate release (sEPSCs) that is independent of CaVs. Here, we tested whether 5-HT3R-sourced calcium contributes to these different forms of glutamate release in horizontal NTS slices from rats. The 5-HT3R selective agonist, m-chlorophenyl biguanide hydrochloride (PBG), enhanced sEPSCs and/or delayed the arrival times of ST-EPSCs (i.e. increased latency). The specific 5-HT3R antagonist, ondansetron, attenuated these effects consistent with direct activation of 5-HT3Rs. PBG did not alter ST-EPSC amplitude or asynchronous EPSCs. These independent actions suggest two distinct 5-HT3R locations; axonal expression that impedes conduction and terminal expression that mobilizes a spontaneous vesicle pool. Calcium chelation with EGTA-AM attenuated the frequency of 5-HT3R-activated sEPSCs by half. The mixture of chelation-sensitive and resistant sEPSCs suggests that 5-HT3R-activated vesicles span calcium diffusion distances that are both distal (micro-) and proximal (nanodomains) to the channel. Our results demonstrate that the calcium domains of 5-HT3Rs do not overlap other calcium sources or their respective vesicle pools. 5-HT3Rs add a unique calcium source on ST afferents as part of multiple independent synaptic signaling mechanisms.