A novel postsynaptic group II metabotropic glutamate receptor role in modulating baroreceptor signal transmission.
A novel postsynaptic group II metabotropic glutamate receptor role in modulating baroreceptor signal transmission.
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DOI：
10.1523/jneurosci.2617-09.2009
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发表时间：
2009-09-23
期刊：
影响因子：
--
通讯作者：
Bonham AC
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文献类型：
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作者：
Sekizawa S;Bechtold AG;Tham RC;Bonham AC
孤束核（NTS）是协调压力反射控制血压的关键。当血压发生变化时，通过谷氨酸与二级压力感受器神经元上的离子型谷氨酸受体结合，压力感受器传入纤维将信息传递到中枢网络。谷氨酸还激活突触前II组和III组代谢型谷氨酸受体（mGluRs），抑制谷氨酸和GABA的释放以调节压力感受器信号传递。在这里，我们提出了一个新的作用，突触后第二组mGluRs进一步微调压力感受器信号传输在第一个中央突触。在脑干切片与离子型谷氨酸和GABA受体阻断，全细胞膜片钳记录的二级压力感受器神经元显示，两组II mGluR激动剂，诱发浓度依赖性膜超极化。超极化仍然是突触前的贡献时，防止与Cd 2 +;被阻止的G-蛋白信号传导抑制剂的细胞内透析的突触后干预;模仿由孤束刺激内源性释放谷氨酸，并防止由第二组mGluR拮抗剂。通过荧光共聚焦免疫组织化学和光学显微镜证实了II组mGluRs的突触后定位。第二组mGluR诱导的电流由电压依赖性外向和内向成分组成，分别由TEA和TTX阻止。与第二组mGluR诱导的超极化相反，对内在兴奋性没有影响，这是由动作电位形状或响应去极化电流注射的放电决定的。这些数据表明，一种新的机制，突触后II组mGluRs微调压力感受器信号传输的NTS。
The nucleus tractus solitarius (NTS) is essential for orchestrating baroreflex control of blood pressure. When a change in blood pressure occurs, the information is transmitted by baroreceptor afferent fibers to the central network by glutamate binding to ionotropic glutamate receptors on second-order baroreceptor neurons. Glutamate also activates presynaptic Group II and III metabotropic glutamate receptors (mGluRs), depressing both glutamate and GABA release to modulate baroreceptor signal transmission. Here we present a novel role for postsynaptic Group II mGluRs to further fine-tune baroreceptor signal transmission at the first central synapses. In a brainstem slice with ionotropic glutamate and GABA receptors blocked, whole-cell patch-clamp recordings of second-order baroreceptor neurons revealed that two Group II mGluR agonists, evoked concentration-dependent membrane hyperpolarizations. The hyperpolarization remained when a presynaptic contribution was prevented with Cd2+; was blocked by a postsynaptic intervention of intracellular dialysis of the G-protein signaling inhibitor; was mimicked by endogenous release of glutamate by tractus solitarius stimulation; and was prevented by a Group II mGluR antagonist. Post-synaptic localization of Group II mGluRs was confirmed by fluorescent confocal immunohistochemistry and light microscopy. Group II mGluR induced-currents consisted of voltage-dependent outward and inward components, prevented by TEA and TTX, respectively. In contrast to Group II mGluR-induced hyperpolarization, there was no effect on intrinsic excitability as determined by action potential shape or firing in response to depolarizing current injections. The data suggest a novel mechanism for postsynaptic Group II mGluRs to fine-tune baroreceptor signal transmission in the NTS.