Interleukin-1β Inhibits The Current Of Large Conductance Ca2+-activated Potassium Channels In Cultured Cortical Neurons Of Rat

Interleukin-1β(IL-1β) is an important porinflammatory cytokine that exert widely biology functions in central nervous system (CNS). Many Studies had reported that the effects of IL-1βwere complicated. These effects include both of neuroprotective and neurotoxic effects in different models or conditions. Voltage-gated K+ channels contribute to the excitability of neurons, and regulate shape of action potential. Large-conductance Ca2+-activated potassium (BK) channels are an important K+ permeable channel with widely distribution, and involved in many cellular functions. Although both of IL-1βand BK channels play key roles in injury and disease of brain, so far the relations of them were reported in few studies.In this study, whole cell patch-clamp recording and single-channel recording were used to investigate the effects of IL-1β(10 ng/mL) treatment for 8 and 24 hours on voltage-dependent K+ currents of cultured cortical neurons from rats. Then we studied the effects,mechanism of action and Physiological significance of whole-cell BK currents by 10 ng/mL of IL-1βtreatment for 24 hours.The results as follow:In this study,we recording the transient outward potassium current , The results showed that the whole cell K+ currents in cortical neurons were not affected by IL-1βtreatment for 8 hours, but significantly inhibited by treatment for 24 hours. Our results suggested that the voltage-gated K+ currents were inhibited by IL-1βtreatment in time dependent manner in cortical neurons of rats.Then it was observed that whole-cell BK currents were inhibited about 30% by 10 ng/mL of IL-1βtreatment for 24 hours.We used inside-out and cell-attached patch clamp recording technique to explore the reason for inhibition of BK currents by IL-1β. In our experiments, it was observed that neither density in membrane nor properties of unitary BK channel was affected by IL-1βtreatment. There were biggish but not significantly difference in conditional NPO and channel density of cell-attached patches between control and IL-1βtreated groups. But these data implicated that the reduction of VGCCs result from IL-1βmay be decrease the functional BK channels in membrane through reduction of Ca2+ source. The data from whole-cell currents recording with antagonist of VGCCs and BK channel supported further this hypothesis.This inhibition of BK currents leads to change of APs conformation and extension of refractory period. These datas indicated that IL-1βable to influence the basic electrical characteristics and thereby regulates neuronal excitability, and extended the knowledge relationship between cytokine and functions of nerve system.