Characterization of persistent TTX-R Na+ currents in physiological concentration of sodium in rat visceral afferents.
Characterization of persistent TTX-R Na+ currents in physiological concentration of sodium in rat visceral afferents.
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DOI：
10.7150/ijbs.5.293
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发表时间：
2009
影响因子：
9.2
通讯作者：
Schild JH
中科院分区：
文献类型：
--
作者：
Qiao GF;Li BY;Zhou YH;Lu YJ;Schild JH
尽管在存在 PGE2 或毛喉素的情况下观察到该电流的功能表达，但在具有 50 mM 细胞外 Na+ 的迷走神经传入神经元 (VAN) 中通常不会记录持续的河豚毒素抗性 (TTX-R) Na+ (Nav1.9/SCN11A) 电流。然而，尚不确定在生理条件下（150 mM Na+）是否可以看到该电流。使用全细胞膜片钳技术，我们发现在 38 个浸入 150 mM Na+ 的 VAN 中，有 9 个表达持续的 TTX-R Na+ 电流。在表达 Nav1.9 的 VAN 中，电流密度显着增强，但全细胞电容没有显着增强。与 TTX 敏感（TTX-S，-40 mV）和 TTX-R Na+ 通道（-20 mV）相比，持续 TTX-R Na+ 通道在接近 -60 mV 的超极化膜电位下被激活。这表明持续的 TTX-R Na+ 通道比 TTX-S 和 TTX-R Na 通道提供更宽的激活窗口来上调神经元兴奋性。这些结果表明，持续的TTX-R Na+电流可能通过设置VAN的较低压力放电阈值和较高的放电频率来参与神经元兴奋性，特别是我们之前的研究中发现的有髓Ah型VAN的独特子集和性别特异性分布，包括Ah型主动脉压力感受器神经元。
Persistent tetrodotoxin-resistant (TTX-R) Na+ (Nav1.9/SCN11A) currents are not normally recorded in vagal afferent neurons (VANs) with 50 mM of extracellular Na+ although the functional expression of this current was observed in the presence of PGE2 or forskolin. However, it is uncertain whether this current can be seen under physiological condition (150 mM Na+). Using the whole-cell patch-clamp technique, we showed that persistent TTX-R Na+ currents were expressed in 9 out of 38 VANs bathed in 150 mM Na+. The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9. Persistent TTX-R Na+ channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na+ channels (at -20 mV). This indicates that persistent TTX-R Na+ channels provide a wider activation window than TTX-S and TTX-R Na channels to up-regulate neuronal excitability. These results suggest that the persistent TTX-R Na+ currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.