Zalicus Pharmaceuticals Ltd, Vancouver, BC, Canada.
Mol Pain. 2011 Sep 12;7:67. doi: 10.1186/1744-8069-7-67.
Voltage-gated sodium channels play key roles in acute and chronic pain processing. The molecular, biophysical, and pharmacological properties of sodium channel currents have been extensively studied for peripheral nociceptors while the properties of sodium channel currents in dorsal horn spinal cord neurons remain incompletely understood. Thus far, investigations into the roles of sodium channel function in nociceptive signaling have primarily focused on recombinant channels or peripheral nociceptors. Here, we utilize recordings from lamina I/II neurons withdrawn from the surface of spinal cord slices to systematically determine the functional properties of sodium channels expressed within the superficial dorsal horn.
Sodium channel currents within lamina I/II neurons exhibited relatively hyperpolarized voltage-dependent properties and fast kinetics of both inactivation and recovery from inactivation, enabling small changes in neuronal membrane potentials to have large effects on intrinsic excitability. By combining biophysical and pharmacological channel properties with quantitative real-time PCR results, we demonstrate that functional sodium channel currents within lamina I/II neurons are predominantly composed of the NaV1.2 and NaV1.3 isoforms.
Overall, lamina I/II neurons express a unique combination of functional sodium channels that are highly divergent from the sodium channel isoforms found within peripheral nociceptors, creating potentially complementary or distinct ion channel targets for future pain therapeutics.
电压门控钠离子通道在急性和慢性疼痛处理中发挥着关键作用。已经对周围伤害感受器的钠离子通道电流的分子、生物物理和药理学特性进行了广泛研究，而脊髓背角神经元中钠离子通道电流的特性仍不完全清楚。到目前为止，对钠离子通道功能在伤害性信号传递中的作用的研究主要集中在重组通道或周围伤害感受器上。在这里，我们利用从脊髓切片表面撤回的 I/II 层神经元的记录，系统地确定在浅层背角中表达的钠离子通道的功能特性。
I/II 层神经元中的钠离子通道电流表现出相对超极化的电压依赖性特性以及失活和失活后恢复的快速动力学，使神经元膜电位的微小变化对固有兴奋性产生很大影响。通过将生物物理和药理学通道特性与定量实时 PCR 结果相结合，我们证明 I/II 层神经元中的功能性钠离子通道电流主要由 NaV1.2 和 NaV1.3 异构体组成。
总体而言，I/II 层神经元表达了一种独特的功能性钠离子通道组合，与周围伤害感受器中的钠离子通道异构体高度不同，为未来的疼痛治疗创造了潜在的互补或独特的离子通道靶点。
