Nav1.9 is of interest to the pain community for a number of reasons, including the human mutations in the gene encoding Nav1.9, SCN11a, that are associated with both pain and loss of pain phenotypes. However, because much of what we know about the biophysical properties of Nav1.9 has been learned through the study of rodent sensory neurons, and there is only 76% identity between human and rodent homologs of SCN11a, there is reason to suggest that there may be differences in the biophysical properties of the channels in human and rodent sensory neurons, and consequently, the contribution of these channels to the control of sensory neuron excitability, if not pain. Thus, the purpose of this study was to characterize Nav1.9 currents in human sensory neurons and compare the properties of these currents with those in rat sensory neurons recorded under identical conditions. Whole-cell patch clamp techniques were used to record Nav1.9 currents in isolated sensory neurons in vitro. Our results indicate that several of the core biophysical properties of the currents, including persistence and a low threshold for activation, are conserved across species. However, we noted a number of potentially important differences between the currents in human and rat sensory neurons including a lower threshold for activation, higher threshold for inactivation, slower deactivation, and faster recovery from slow inactivation. Human Nav1.9 was inhibited by inflammatory mediators, whereas rat Nav1.9 was potentiated. Our results may have implications for the role of Nav1.9 in sensory, if not nociceptive signaling.

中文翻译：

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人背根神经节神经元中的持续 （Nav1.9） 钠电流。


Nav1.9 引起疼痛界的兴趣有很多，包括编码 Nav1.9 、 SCN11a 的基因中的人类突变，这与疼痛和疼痛表型的丧失有关。然而，由于我们对 Nav1.9 的生物物理特性的大部分了解都是通过对啮齿动物感觉神经元的研究了解的，并且 SCN11a 的人类和啮齿动物同源物之间只有 76% 的同一性，因此有理由表明人类和啮齿动物感觉神经元中通道的生物物理特性可能存在差异， 因此，这些通道对控制感觉神经元兴奋性（如果不是疼痛）的贡献。因此，本研究的目的是表征人类感觉神经元中的 Nav1.9 电流，并将这些电流的特性与在相同条件下记录的大鼠感觉神经元中的电流进行比较。全细胞膜片钳技术用于在体外记录离体感觉神经元中的 Nav1.9 电流。我们的结果表明，电流的几个核心生物物理特性，包括持久性和低激活阈值，在物种之间是保守的。然而，我们注意到人类和大鼠感觉神经元中的电流之间存在许多潜在的重要差异，包括较低的激活阈值、较高的失活阈值、较慢的失活速度以及从缓慢失活中恢复的速度更快。人 Nav1.9 被炎症介质抑制，而大鼠 Nav1.9 被增强。我们的结果可能对 Nav1.9 在感觉（如果不是伤害性信号传导）中的作用产生影响。