TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and regulates pain processing.
TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and regulates pain processing.
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DOI：
10.1038/nn.3468
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发表时间：
2013-09
影响因子：
25
通讯作者：
Jan, Lily Yeh
中科院分区：
文献类型：
--
作者：
Huang, Fen;Wang, Xidao;Ostertag, Eric M.;Nuwal, Tulip;Huang, Bo;Jan, Yuh-Nung;Basbaum, Allan I.;Jan, Lily Yeh
TMEM 16 C属于TMEM 16家族，其包括Ca 2+激活的Cl-通道（CaCC）TMEM 16 A和TMEM 16 B以及小电导Ca 2+激活的非选择性阳离子通道（SCAN）TMEM 16 F。在这里，我们报告说，在大鼠背根神经节（DRG）TMEM 16 C主要表达在IB 4阳性，非肽能伤害感受器，也表达钠激活钾（KNa）通道松弛。这些通道蛋白共同促进KNa通道活性并抑制神经元兴奋性。来自TMEM 16 C敲除大鼠的DRG具有减少的Slack表达、加宽的动作电位和增加的兴奋性。此外，TMEM 16 C敲除大鼠以及通过鞘内注射siRNA的Slack敲减的大鼠表现出增加的热敏感性和机械敏感性。涉及HEK 293细胞中异源表达的实验进一步显示TMEM 16 C调节Slack通道的单通道活性并增加其钠敏感性。因此，我们的研究表明，TMEM 16 C增强DRG神经元的KNa通道活性，并调节疼痛信息的处理。
TMEM16C belongs to the TMEM16 family, which includes the Ca2+-activated Cl– channels (CaCCs) TMEM16A and TMEM16B and a small conductance Ca2+-activated, non-selective cation channel (SCAN), TMEM16F. Here we report that in rat dorsal root ganglia (DRG) TMEM16C is expressed mainly in the IB4 positive, non-peptidergic nociceptors that also express the sodium-activated potassium (KNa) channel Slack. Together these channel proteins promote KNa channel activity and dampen neuronal excitability. DRG from TMEM16C knock out rats have reduced Slack expression, broadened action potential and increased excitability. Moreover, the TMEM16C knock out rats as well as rats with Slack knockdown via intrathecal injection of siRNA exhibit increased thermal and mechanical sensitivity. Experiments involving heterologous expression in HEK293 cells further show that TMEM16C modulates the single channel activity of Slack channels and increases its sodium sensitivity. Our study thus reveals that TMEM16C enhances KNa channel activity in DRG neurons and regulate the processing of pain messages.
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作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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