Distinct cellular expression and subcellular localization of Kv2 voltage-gated K+ channel subtypes in dorsal root ganglion neurons conserved between mice and humans.
Distinct cellular expression and subcellular localization of Kv2 voltage-gated K+ channel subtypes in dorsal root ganglion neurons conserved between mice and humans.
复制标题
小鼠和人类之间保守的背根神经节神经元中 Kv2 电压门控 K 通道亚型的独特细胞表达和亚细胞定位。
DOI：
10.1101/2023.03.01.530679
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Sack,JonT
中科院分区：
文献类型：
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作者：
Stewart,RobertG;Camacena,Miriam;Copits,BryanA;Sack,JonT
Kv2电压门控钾通道在脑神经元细胞体及其附近的独特结构使其能够调节动作电位和特殊的膜接触部位。体感神经元具有假单极的形态，通过分支到脊髓和神经节内的细胞体(包括背根神经节)的轴突将动作电位从周围神经末梢传递到神经节。Kv2通道调节体感神经元的动作电位，但对Kv2通道的位置知之甚少。在这里，我们用一组抗体、细胞标记物和转基因小鼠定义了Kv2类似物Kv2.1和Kv2.2在DRG躯体感觉神经元中的细胞和亚细胞定位。我们发现，相对于脊髓神经元，DRG神经元具有相似的可检测到的Kv2.1水平和更高的Kv2.2水平。在老年小鼠中，可检测到的Kv2.2保持不变，而可检测到的Kv2.1降低。这两种Kv2亚型都采用了不同于中枢神经元的簇状亚细胞模式。大多数DRG神经元共表达Kv2.1和Kv2.2，但神经元亚群优先表达Kv2.1或Kv2.2。我们发现Kv2蛋白在小鼠和人背根神经节神经元中的表达和亚细胞定位相似。我们的结论是，这两个Kv2通道的组织与DRG神经元的体细胞和干轴突中的生理作用是一致的。与中枢神经元相比，Kv2.2在DRG中的普遍流行，以及Kv2.2在老年小鼠、本体感受器和轴突中相对于可检测到的Kv2.1的丰富，表明Kv2.2在DRG神经元中发挥着更广泛的作用。
The distinct organization of Kv2 voltage‐gated potassium channels on and near the cell body of brain neurons enables their regulation of action potentials and specialized membrane contact sites. Somatosensory neurons have a pseudounipolar morphology and transmit action potentials from peripheral nerve endings through axons that bifurcate to the spinal cord and the cell body within ganglia including the dorsal root ganglia (DRG). Kv2 channels regulate action potentials in somatosensory neurons, yet little is known about where Kv2 channels are located. Here, we define the cellular and subcellular localization of the Kv2 paralogs, Kv2.1 and Kv2.2, in DRG somatosensory neurons with a panel of antibodies, cell markers, and genetically modified mice. We find that relative to spinal cord neurons, DRG neurons have similar levels of detectable Kv2.1 and higher levels of Kv2.2. In older mice, detectable Kv2.2 remains similar, while detectable Kv2.1 decreases. Both Kv2 subtypes adopt clustered subcellular patterns that are distinct from central neurons. Most DRG neurons co‐express Kv2.1 and Kv2.2, although neuron subpopulations show preferential expression of Kv2.1 or Kv2.2. We find that Kv2 protein expression and subcellular localization are similar between mouse and human DRG neurons. We conclude that the organization of both Kv2 channels is consistent with physiological roles in the somata and stem axons of DRG neurons. The general prevalence of Kv2.2 in DRG as compared to central neurons and the enrichment of Kv2.2 relative to detectable Kv2.1 in older mice, proprioceptors, and axons suggest more widespread roles for Kv2.2 in DRG neurons.