Relief from chronic pain continues to represent a large unmet need. The voltage-gated potassium channel Kv7.2/7.3, also known as KCNQ2/3, is a key contributor to the control of resting membrane potential and excitability in nociceptive neurons and represents a promising target for potential therapeutics. In this study, we present a medium throughput electrophysiological assay for the identification and characterization of modulators of Kv7.2/7.3 channels, using the IonWorks Barracuda™ automated voltage clamp platform. The assay combines a family of voltage steps used to construct conductance curves with a unique analysis method. Kv7.2/7.3 modulators shift the activation voltage and/or change the maximal conductance of the current, and both parameters have been used to quantify compound mediated effects. Both effects are expected to modulate neuronal excitability in vivo. The analysis method described assigns a single potency value that combines changes in activation voltage and maximal conductance and is expected to predict compound mediated changes in excitability.

中文翻译：

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在IonWorks梭子鱼上开发Kv7调节剂的电生理检测方法。

缓解慢性疼痛仍然是未满足的巨大需求。电压门控钾通道Kv7.2 / 7.3，也称为KCNQ2 / 3，是伤害性神经元中静息膜电位和兴奋性控制的关键因素，并代表了潜在疗法的有希望的靶点。在这项研究中，我们使用IonWorks Barracuda™自动电压钳位平台，提出了一种中等通量电生理测定法，用于鉴定和表征Kv7.2 / 7.3通道的调节剂。该测定法结合了用于构建电导曲线的一系列电压步骤和独特的分析方法。Kv7.2 / 7.3调制器可移动激活电压和/或改变电流的最大电导率，并且两个参数均已用于量化化合物介导的作用。预期这两种作用都会调节体内神经元兴奋性。所描述的分析方法分配了一个单独的效价值，该值结合了激活电压和最大电导率的变化，并有望预测化合物介导的兴奋性变化。