Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA; Neuroscience Training Program, Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Neuron. 2019 Aug 21;103(4):598-616.e7. doi: 10.1016/j.neuron.2019.05.039. Epub 2019 Jun 24.
Dorsal root ganglion (DRG) sensory neuron subtypes defined by their in vivo properties display distinct intrinsic electrical properties. We used bulk RNA sequencing of genetically labeled neurons and electrophysiological analyses to define ion channel contributions to the intrinsic electrical properties of DRG neuron subtypes. The transcriptome profiles of eight DRG neuron subtypes revealed differentially expressed and functionally relevant genes, including voltage-gated ion channels. Guided by these data, electrophysiological analyses using pharmacological and genetic manipulations as well as computational modeling of DRG neuron subtypes were undertaken to assess the functions of select voltage-gated potassium channels (Kv1, Kv2, Kv3, and Kv4) in shaping action potential (AP) waveforms and firing patterns. Our findings show that the transcriptome profiles have predictive value for defining ion channel contributions to sensory neuron subtype-specific intrinsic physiological properties. The distinct ensembles of voltage-gated ion channels predicted to underlie the unique intrinsic physiological properties of eight DRG neuron subtypes are presented.
背根神经节 (DRG) 感觉神经元亚型根据其体内特性定义，表现出明显不同的内在电生理特性。我们使用遗传标记神经元的批量 RNA 测序和电生理分析来定义离子通道对 DRG 神经元亚型内在电生理特性的贡献。八种 DRG 神经元亚型的转录组谱揭示了差异表达和功能相关的基因，包括电压门控离子通道。根据这些数据，我们使用药理学和遗传学方法进行电生理分析，并对 DRG 神经元亚型进行计算建模，以评估选定的电压门控钾通道 (Kv1、Kv2、Kv3 和 Kv4) 在塑造动作电位 (AP) 波形和放电模式方面的功能。我们的研究结果表明，转录组谱对于确定离子通道对感觉神经元亚型特异性内在生理特性的贡献具有预测价值。呈现了预测为八个 DRG 神经元亚型独特内在生理特性提供基础的不同电压门控离子通道集合。
