Interleukin-1β Inhibits Voltage-Gated Sodium Currents in a Time- and Dose-Dependent Manner in Cortical Neurons

Abstract

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.

Glial responses to implanted electrodes in the brain

“…Alterations in channel currents may occur on both short- and long-term timescales, where short-term effects are most probably attributed to alterations in gating characteristics or post-translational modifications to channel proteins, whereas longer-term impacts may be related to changes in channel expression 84 . Acute effects (within 24 hours) tend to favour hyperexcitability, whereas longer-term impacts (days or weeks after exposure or injury) tend to favour loss of excitatory sodium 85,86 and calcium currents 87,88 in the CNS, a trend that has been interpreted as the progressive dampening of the excitability of affected neurons to promote neuroprotection and prevent excitotoxicity 89 . Impaired excitability would limit the detection of neuronal activity by investigational recording devices and elevate the stimulation thresholds required for clinical neuromodulation devices.…”

The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron Responses to TRPV1 by Activation of TLR4

“…The sustained activity of these proinflammatory cytokines could well underlie the more chronic responses of DRG and spinal neurons observed here. For example, IL-1␤ was shown to activate voltage-gated calcium channels and to inhibit voltagegated sodium channels Zhou et al, 2011). Conversely, TNF-␣ upregulates the voltage-gated sodium channels Nav1.3 and Nav1.8 (He et al, 2010).…”

Acute lipopolysaccharide exposure facilitates epileptiform activity via enhanced excitatory synaptic transmission and neuronal excitability in vitro

“…Inflammatory mediators yielded after LPS application are various and have complicated effects on ion channels. For example, IL-1β can activate voltage-gated Ca 2+ channels29 and inhibit voltage-gated Na + channels 30. TNF-α can up-regulate voltage-gated sodium channel (Nav)1.3 and Nav1.8, which increase sodium ion influx 31.…”