Interleukin-1β Inhibits Voltage-Gated Sodium Currents in a Time- and Dose-Dependent Manner in Cortical Neurons
- 241 Downloads
Interleukin-1β (IL-1β) is a multifunctional proinflammatory cytokine that plays a key role in the injuries and diseases of the central nervous system (CNS). A voltage-gated Na+ channel is essential for the excitability and electrical properties of neurons. However, it is not known whether IL-1β directly affects the central Na+ channels. In the present study, we examined the effects of IL-1β on Na+ currents in cultured cortical neurons using patch-clamp recording. Our results showed that IL-1β suppressed Na+ currents through its receptor in a time- and dose-dependent manner, but did not alter the voltage-dependent activation and inactivation. PKC and then p38 MAPK were involved in this inhibition. The spike amplitude was also inhibited by IL-1β in the doses that decreased the Na+ currents. Our findings revealed the inhibition of chronic IL-1β treatment on voltage-gated Na+ channels in the CNS, and showed that the action potential (AP) amplitude was reduced by IL-1β due to a decrease of Na+ currents.
KeywordsInterleukin-1β Voltage-gated sodium currents Cortical neurons Patch-clamp recording
This work was supported by National Key Basis Research Program of Ministry of Science and Technology of China (973 grant number: 2006CB504105 and 2009CB941301) and National Natural Science Foundation of China (grant number: 30670500 and 30871287).
- 7.Goldfarb M, Schoorlemmer J, Williams A, Diwakar S, Wang Q, Huang X, Giza J, Tchechik D, Kelley K, Vega A, Matthews G, Rossi P, Ornitz DM, D’Angelo E (2007) Fibroblast growth factor homologous factors control neuronal excitability through modulation of voltage-gated sodium channels. Neuron 55:449–463PubMedCrossRefGoogle Scholar
- 11.Momin A, Wood JN (2008) Sensory neuron voltage-gated sodium channels as analgesic drug targets. Curr Opin Neurol 18:383–388Google Scholar
- 16.Plata-Salamán CR, ffrench-Mullen JMH (1992) Interleukin-1β depresses calcium currents in CA1 hippocampal neurons at pathophysiological concentration. Brain Res 29:221–223Google Scholar
- 17.Roux J, Kawakatsu H, Gartland B, Pespeni M, Sheppard D, Matthay MA, Canessa CM, Pittet J (2005) Interleukin-1β decreases expression of the epithelial sodium channel α-subunit in alveolar epithelial cell via a p38 MAPK-dependent signaling pathway. J Biol Chem 280:18579–18589PubMedCrossRefGoogle Scholar
- 20.Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartfai T, Binaglia M, Corsini M, Luca D, Galli CL, Marinovich M (2003) Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the src family of kinases. J Neurosci 23(25):8692–8700PubMedGoogle Scholar