Acid-sensing ion channel 1 and nitric oxide synthase are in adjacent layers in the wall of rat and human cerebral arteries.

Acid-sensing ion channel 1 and nitric oxide synthase are in adjacent layers in the wall of rat and human cerebral arteries.
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DOI:
10.1016/j.jchemneu.2014.10.002
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发表时间:
2014-11
影响因子:
2.8
通讯作者:
Talman WT
Talman WT
中科院分区:
医学4区
文献类型:
--
作者:
Lin LH;Jin J;Nashelsky MB;Talman WT

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胞外酸化激活一种称为酸敏离子通道(ASICs)的蛋白质家族。ASIC亚型ASIC 1(ASIC1)可能在突触可塑性、记忆、恐惧条件反射和缺血性脑损伤中发挥重要作用。ASIC1主要在神经元中发现,但一份报告显示它在分离的小鼠脑血管细胞中表达。在这项研究中,我们试图确定ASIC1是否存在于完整的大鼠和人的主要大脑动脉中。研究表明,一氧化氮(NO)作为一种强大的血管扩张剂,可能调节表达ASIC1的培养细胞的质子门控电流,这一发现具有潜在的生理意义。由于构成一氧化氮合成酶的神经元型一氧化氮合酶(NNOS)和内皮型一氧化氮合酶(ENOS)在脑动脉中均有表达,因此我们还研究了ASIC1与nNOS或eNOS在大鼠和人脑动脉中的解剖关系。Western印迹分析显示,这两个物种的脑动脉中都有ASIC1。免疫荧光组织化学和共聚焦显微镜也显示ASIC1免疫反应阳性(IR)存在于大鼠和人的大脑前动脉(ACA)、大脑中动脉(MCA)、大脑后动脉(PCA)和基底动脉(BA),并与平滑肌标志物α-平滑肌肌动蛋白(SMA)共存。ASIC1在大鼠和人脑动脉中的表达与ASIC1在调节脑血管张力中的作用一致。邻近血管外膜层存在nNOS-IR,邻近内皮层存在nNOS-IR和eNOS-IR,支持平滑肌ASIC1与nNOS或eNOS之间的潜在相互作用。
Extracellular acidification activates a family of proteins known as acid-sensing ion channels (ASICs). One ASIC subtype, ASIC type 1 (ASIC1), may play an important role in synaptic plasticity, memory, fear conditioning and ischemic brain injury. ASIC1 is found primarily in neurons, but one report showed its expression in isolated mouse cerebrovascular cells. In this study, we sought to determine if ASIC1 is present in intact rat and human major cerebral arteries. A potential physiological significance of such a finding is suggested by studies showing that nitric oxide (NO), which acts as a powerful vasodilator, may modulate proton-gated currents in cultured cells expressing ASIC1s. Because both constitutive NO synthesizing enzymes, neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS), are expressed in cerebral arteries we also studied the anatomical relationship between ASIC1 and nNOS or eNOS in both rat and human cerebral arteries. Western blot analysis demonstrated ASIC1 in cerebral arteries from both species. Immunofluorescent histochemistry and confocal microscopy also showed that ASIC1-immunoreactivity (IR), colocalized with the smooth muscle marker alpha-smooth muscle actin (SMA), was present in the anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) and basilar artery (BA) of rat and human. Expression of ASIC1 in cerebral arteries is consistent with a role for ASIC1 in modulating cerebrovascular tone both in rat and human. Potential interactions between smooth muscle ASIC1 and nNOS or eNOS were supported by the presence of nNOS-IR in the neighboring adventitial layer and the presence of nNOS-IR and eNOS-IR in the adjacent endothelial layer of the cerebral arteries.
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