Nav1.7 is the predominant sodium channel in rodent olfactory sensory neurons.

Nav1.7 is the predominant sodium channel in rodent olfactory sensory neurons.
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DOI:
10.1186/1744-8069-7-32
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发表时间:
2011-05-10
期刊:
影响因子:
3.3
通讯作者:
Dib-Hajj SD
Dib-Hajj SD
中科院分区:
医学3区
文献类型:
--
作者:
Ahn HS;Black JA;Zhao P;Tyrrell L;Waxman SG;Dib-Hajj SD

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电压门控性钠通道Nav1.7主要表达于外周神经系统内的背根节和交感神经元。编码Nav1.7的基因SCN9A的纯合或复合杂合性功能丧失突变会导致先天性疼痛不敏感(CIP)并伴有嗅觉障碍。据报道,小鼠体内Nav1.7基因的全球敲除是新生儿因饥饿而死亡,这表明存在嗅觉障碍。这些发现使我们假设Nav1.7是外周嗅觉神经元(OSN,也称为嗅觉感受器神经元)的主要钠通道。我们采用多重聚合酶链式反应-限制性内切酶多态、原位杂交和免疫组织化学的方法来确定啮齿动物OSNs中钠通道的特性。我们在这里表明,在大鼠和小鼠的嗅觉上皮细胞中,Nav1.7是主要的钠通道转录本,其他钠通道转录本的丰度很低。我们的原位杂交数据表明,Nav1.7转录本存在于大鼠OSN中。大鼠嗅球周围突触前轴突的Nav1.7和Nav1.6通道呈互补聚集模式,Nav1.6主要分布于中枢神经系统内嗅球肾小球的突触后细胞及其树突。我们的数据显示,在大鼠和小鼠OSN中,Nav1.7是主要的钠通道,这可能解释了Nav1.7基因缺失小鼠和与Nav1.7相关的CIP患者的嗅觉障碍。
Voltage-gated sodium channel Nav1.7 is preferentially expressed in dorsal root ganglion (DRG) and sympathetic neurons within the peripheral nervous system. Homozygous or compound heterozygous loss-of-function mutations in SCN9A, the gene which encodes Nav1.7, cause congenital insensitivity to pain (CIP) accompanied by anosmia. Global knock-out of Nav1.7 in mice is neonatal lethal reportedly from starvation, suggesting anosmia. These findings led us to hypothesize that Nav1.7 is the main sodium channel in the peripheral olfactory sensory neurons (OSN, also known as olfactory receptor neurons). We used multiplex PCR-restriction enzyme polymorphism, in situ hybridization and immunohistochemistry to determine the identity of sodium channels in rodent OSNs. We show here that Nav1.7 is the predominant sodium channel transcript, with low abundance of other sodium channel transcripts, in olfactory epithelium from rat and mouse. Our in situ hybridization data show that Nav1.7 transcripts are present in rat OSNs. Immunostaining of Nav1.7 and Nav1.6 channels in rat shows a complementary accumulation pattern with Nav1.7 in peripheral presynaptic OSN axons, and Nav1.6 primarily in postsynaptic cells and their dendrites in the glomeruli of the olfactory bulb within the central nervous system. Our data show that Nav1.7 is the dominant sodium channel in rat and mouse OSN, and may explain anosmia in Nav1.7 null mouse and patients with Nav1.7-related CIP.
DOI: 10.1073/pnas.1004571107
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