Stewart Robert G, Camacena Miriam, Copits Bryan A, Sack Jon T
Department of Physiology and Membrane Biology, University of California, Davis, Davis, California, USA.
Washington University Pain Center, Washington University School of Medicine, St. Louis, Missouri, USA.
J Comp Neurol. 2024 Feb;532(2):e25575. doi: 10.1002/cne.25575.
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.
脑神经元细胞体上及附近的Kv2电压门控钾通道独特的组织方式,使其能够调节动作电位和特殊的膜接触位点。体感神经元具有假单极形态,可将动作电位从外周神经末梢通过轴突传递至脊髓以及包括背根神经节(DRG)在内的神经节内的细胞体。Kv2通道调节体感神经元的动作电位,但Kv2通道的位置却鲜为人知。在此,我们利用一组抗体、细胞标记物和基因工程小鼠,确定了DRG体感神经元中Kv2旁系同源物Kv2.1和Kv2.2的细胞及亚细胞定位。我们发现,与脊髓神经元相比,DRG神经元中可检测到的Kv2.1水平相似,而Kv2.2水平更高。在老年小鼠中,可检测到的Kv2.2保持相似,而可检测到的Kv2.1则减少。两种Kv2亚型均呈现出与中枢神经元不同的聚集亚细胞模式。大多数DRG神经元共表达Kv2.1和Kv2.2,尽管神经元亚群表现出对Kv2.1或Kv2.2的优先表达。我们发现,小鼠和人类DRG神经元之间的Kv2蛋白表达和亚细胞定位相似。我们得出结论,两种Kv2通道的组织方式与DRG神经元胞体和轴突干中的生理作用一致。与中枢神经元相比,Kv2.2在DRG中普遍存在,并且在老年小鼠、本体感受器和轴突中,Kv2.2相对于可检测到的Kv2.1更为丰富,这表明Kv2.2在DRG神经元中具有更广泛的作用。