1 Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Hunan, China.
2 Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, USA.
Acta Neuropsychiatr. 2014 Jun;26(3):170-7. doi: 10.1017/neu.2013.49.
Interleukin-6 (IL-6) is a pleiotropic proinflammatory cytokine that plays a key role in the injuries and diseases of the central nervous system (CNS). A voltage-gated Na+ channel (VGSC) is essential for the excitability and electrical properties of the neurons. However, there is still limited information on the role of IL-6 in voltage-gated sodium channels. Our study aimed to investigate the effects of IL-6 on Na+ currents in cultured spinal-cord neurons.
VGSC currents were activated and recorded using whole-cell patch-clamp technique in the cultured rat spinal cord neurons. The effects of IL-6 concentration and exposure duration were examined. To determine whether any change in the number of channels in the plasma membrane can inhibit IL-6 on VGSC currents, we examined the expression of α1A (SCN1α) subunit mRNA level and protein level in the neurons before and after IL-6 induction using real-time polymerase chain reaction.
We verified that IL-6, through a receptor-mediated mechanism, suppressed Na+ currents in a time- and dose-dependent manner, but did not alter the voltage-dependent activation and inactivation. Gp130 was involved in this inhibition. Furthermore, the spike amplitude was also inhibited by IL-6 in the doses that decreased the Na+ currents.
VGSC currents are significantly inhibited by IL-6. Our findings reveal that the potential neuroprotection of IL-6 may result from the inhibitory effects on VGSC currents.
白细胞介素 6（IL-6）是一种多功能促炎细胞因子，在中枢神经系统（CNS）的损伤和疾病中发挥关键作用。电压门控钠离子通道（VGSC）对神经元的兴奋性和电特性至关重要。然而，关于 IL-6 在电压门控钠离子通道中的作用的信息仍然有限。我们的研究旨在探讨 IL-6 对培养的脊髓神经元中 Na+电流的影响。
使用全细胞膜片钳技术在培养的大鼠脊髓神经元中激活和记录 VGSC 电流。研究了 IL-6 浓度和暴露时间的影响。为了确定质膜中通道数量的任何变化是否可以抑制 IL-6 对 VGSC 电流的影响，我们使用实时聚合酶链反应在 IL-6 诱导前后检查了神经元中 α1A（SCN1α）亚基 mRNA 水平和蛋白水平的表达。
我们验证了 IL-6 通过受体介导的机制，以时间和剂量依赖的方式抑制 Na+电流，但不改变电压依赖性激活和失活。Gp130 参与了这种抑制。此外，IL-6 还在降低 Na+电流的剂量下抑制了尖峰幅度。
VGSC 电流被 IL-6 显著抑制。我们的发现表明，IL-6 的潜在神经保护作用可能来自于对 VGSC 电流的抑制作用。
