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Voltage gated calcium channels in human dorsal root ganglion neurons.
Pain ( IF 5.9 ) Pub Date : 2021-08-27 , DOI: 10.1097/j.pain.0000000000002465
Jane E Hartung 1 , Jamie K Moy 1 , Emanuel Loeza-Alcocer 1 , Vidhya Nagarajan 1 , Ruth Jostock 2 , Thomas Christoph 2 , Wolfgang Schroeder 2 , Michael S Gold 1
Affiliation  

Voltage gated calcium currents (VGCCs) in sensory neurons underlie processes ranging from neurotransmitter release to gene expression and remain a therapeutic target for the treatment of pain. Yet virtually all we know about VGCCs has been obtained through the study of rodent sensory neurons and heterologously expressed channels. To address this, high voltage activated (HVA) Ca2+ currents in dissociated human and rat dorsal root ganglion (DRG) neurons were characterized with whole cell patch clamp techniques. The HVA currents from both species shared basic biophysical and pharmacological properties. However, HVA currents in human neurons differed from those in the rat in at least three potentially important ways: (1) Ca2+ current density was significantly smaller, (2) the proportion of nifedipine-sensitive currents was far greater, and (3) a subpopulation of human neurons displayed relatively large constitutive current inhibition. These results highlight the need to for the study of native proteins in their native environment prior to initiating costly clinical trials.

中文翻译:

人背根神经节神经元的电压门控钙通道。

感觉神经元中的电压门控钙电流(VGCC)是从神经递质释放到基因表达等过程的基础,并且仍然是疼痛治疗的治疗靶点。然而,实际上我们对 VGCC 的了解都是通过对啮齿动物感觉神经元和异源表达通道的研究获得的。为了解决这个问题,利用全细胞膜片钳技术对分离的人和大鼠背根神经节 (DRG) 神经元中的高压激活 (HVA) Ca2+ 电流进行了表征。两个物种的 HVA 电流具有相同的基本生物物理和药理学特性。然而,人类神经元中的 HVA 电流至少在三个潜在的重要方面不同于大鼠:(1) Ca2+ 电流密度明显较小,(2) 硝苯地平敏感电流的比例要大得多,(3)人类神经元亚群表现出相对较大的本构电流抑制。这些结果强调了在开始昂贵的临床试验之前需要在天然环境中研究天然蛋白质。
更新日期:2021-08-27
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