Zhang Xiulin, Priest Birgit T, Belfer Inna, Gold Michael S
Department of Urology, The Second Hospital of Shandong University, Jinan Shi, China.
Lilly Research Laboratories, Indianapolis, United States.
Elife. 2017 May 16;6:e23235. doi: 10.7554/eLife.23235.
Available evidence indicates voltage-gated Na channels (VGSCs) in peripheral sensory neurons are essential for the pain and hypersensitivity associated with tissue injury. However, our understanding of the biophysical and pharmacological properties of the channels in sensory neurons is largely based on the study of heterologous systems or rodent tissue, despite evidence that both expression systems and species differences influence these properties. Therefore, we sought to determine the extent to which the biophysical and pharmacological properties of VGSCs were comparable in rat and human sensory neurons. Whole cell patch clamp techniques were used to study Na currents in acutely dissociated neurons from human and rat. Our results indicate that while the two major current types, generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were qualitatively similar in neurons from rats and humans, there were several differences that have important implications for drug development as well as our understanding of pain mechanisms.
现有证据表明,外周感觉神经元中的电压门控钠通道(VGSCs)对于与组织损伤相关的疼痛和超敏反应至关重要。然而,尽管有证据表明表达系统和物种差异都会影响这些特性,但我们对感觉神经元中这些通道的生物物理和药理学特性的了解很大程度上基于异源系统或啮齿动物组织的研究。因此,我们试图确定大鼠和人类感觉神经元中VGSCs的生物物理和药理学特性具有可比性的程度。采用全细胞膜片钳技术研究人和大鼠急性解离神经元中的钠电流。我们的结果表明,虽然大鼠和人类神经元中通常称为河豚毒素(TTX)敏感型和TTX抵抗型的两种主要电流类型在性质上相似,但仍存在一些差异,这些差异对药物开发以及我们对疼痛机制的理解具有重要意义。