The Effects Of Interleukin-1β On Sodium Current And Action Potential In Cortical Neurons Of Rats

Interleukin-1β(IL-1β) is an important porinflammatory cytokine that exerts key roles in injuries and diseases of the central nervous system (CNS). Voltage-gated Na+ channel is the most important ion channel of neurons, and is essential for regenerative action potential (AP). The Na+ channel also contribute to many diseases of brain. However, so far their relations between IL-1βand central Na+ channel were not reported. In this study, whole cell patch-clamp recording was used to investigate the acute effects of IL-1β(10 ng/mL) on voltage-dependent Na+ currents and AP of cultured cortical neurons from rats. Results showed that the half-activation voltage of Na+ channels and the threshold of AP, but not the amplitude, slope factor of activation, and inactivation properties, were affected by IL-1β. These data suggested that increased IL-1βin injury and disease may upregulate the excitability of neurons, and thereby exacerbate the neurotoxicity.In order to understand the effect of IL-1βon CNS, we continue to research the chronic effect of IL-1βon cortical neurons of the central nervous system for the sodium current and action potential. Our results showed that IL-1βsuppressed Na+ currents through its receptor in a time- and dose-dependent manner, but did not alter the voltage-dependent activation and inactivation. We then investigated the mechanism of this effect, and found that PKC and p38 MAPK were involved in this inhibition. It can be deduced that IL-1βmay also inhibits the expression of the sodium channel in cortical neurons, thereby reducing the current amplitude.Current-clamp recording was used to analyze the effect of IL-1βon the action potential. And the results were consistent with voltage clamp recording, current clamp recording showed that IL-1βreduces the amplitude of action potential but not the threshold. These results indicate that prolonged IL-1βtreatment can inhibits the voltage-gated sodium current, this inhibition reduced the amplitude of action potential, which may change the electrical properties, synaptic transmission and other basic functions of neurons, the results also provide us the new thinking of the roles that IL-1βplayed in the injury and disease of nervous system. Synaptic transmission is the way the nervous system to complete its function, the action potentials of presynaptic neurons determines the number of transmitter release, which determines the response of the postsynaptic neurons. Patch clamp recording was used to investigate the spontaneous postsynaptic currents, and the amplitude of IL-1βtreatment reduces by about 15%. The results showed that IL-1βtreatment is likely to reduce the postsynaptic response by inhibiting the action potential. These effects provided us a new thinking of the effect of IL-1βin the central nervous system, that is it can affect the electrical properties of neurons throngh the ion channel.