Nalcn Is a "Leak" Sodium Channel That Regulates Excitability of Brainstem Chemosensory Neurons and Breathing
Nalcn Is a "Leak" Sodium Channel That Regulates Excitability of Brainstem Chemosensory Neurons and Breathing
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DOI：
10.1523/jneurosci.1096-16.2016
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发表时间：
2016-08-03
影响因子：
5.3
通讯作者：
Bayliss, Douglas A.
中科院分区：
文献类型：
--
作者：
Shi, Yingtang;Abe, Chikara;Bayliss, Douglas A.
背景钾和钠通道的活性决定了神经元的兴奋性，但“泄漏”Na+通道在特定哺乳动物神经元中的生理作用尚未确定。在这里，我们发现泄漏Na+通道Nalcn在调节呼吸的小鼠后梯形核（RTN）的CO2/H+敏感神经元中表达。在RTN神经元中，Nalcn的表达与碱化程度较高的动作电位放电相关；shrna介导的Nalcn超极化RTN神经元耗竭，降低漏Na+电流和放电速率。Nalcn消耗也降低了神经肽P物质对RTN神经元的激活，而不影响ph敏感的背景K+电流或共递素5 -羟色胺的激活。在体内，rtn特异性敲低Nalcn可减少二氧化碳诱发的神经元激活和呼吸；低氧过度通气无变化。因此，Nalcn调节RTN神经元的兴奋性和二氧化碳刺激，独立于直接的pH感应，可能有助于Nalcn突变的呼吸效应；Nalcn的递质调节可能是呼吸和呼吸化学敏感性的状态依赖性变化的基础。
The activity of background potassium and sodium channels determines neuronal excitability, but physiological roles for "leak" Na+ channels in specific mammalian neurons have not been established. Here, we show that a leak Na+ channel, Nalcn, is expressed in the CO2/H+-sensitive neurons of the mouse retrotrapezoid nucleus (RTN) that regulate breathing. In RTN neurons, Nalcn expression correlated with higher action potential discharge over a more alkalized range of activity; shRNA-mediated depletion of Nalcn hyperpolarized RTN neurons, and reduced leak Na+ current and firing rate. Nalcn depletion also decreased RTN neuron activation by the neuropeptide, substance P, without affecting pH-sensitive background K+ currents or activation by a cotransmitter, serotonin. In vivo, RTN-specific knockdown of Nalcn reduced CO2-evoked neuronal activation and breathing; hypoxic hyperventilation was unchanged. Thus, Nalcn regulates RTN neuronal excitability and stimulation by CO2, independent of direct pH sensing, potentially contributing to respiratory effects of Nalcn mutations; transmitter modulation of Nalcn may underlie state-dependent changes in breathing and respiratory chemosensitivity.