Interleukin-1ß inhibits voltage-gated sodium currents in a time- and dose-dependent manner in cortical neurons.

ABSTRACT

Interleukin-1ß (IL-1ß) 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-1ß directly affects the central Na(+) channels. In the present study, we examined the effects of IL-1ß on Na(+) currents in cultured cortical neurons using patch-clamp recording. Our results showed that IL-1ß 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-1ß in the doses that decreased the Na(+) currents. Our findings revealed the inhibition of chronic IL-1ß treatment on voltage-gated Na(+) channels in the CNS, and showed that the action potential (AP) amplitude was reduced by IL-1ß due to a decrease of Na(+) currents.