Interleukin-1beta downregulates the L-type Ca2+ channel activity by depressing the expression of channel protein in cortical neurons.

Interleukin-1beta (IL-1beta), a proinflammatory cytokine, has been involved in various diseases of the central nervous system (CNS). Due to the diverse, "contradictory" effects of IL-1beta on neurons during insults to the brain, the mechanisms underlying these effects have not been elucidated. Calcium influx through the L-type Ca2+ channels (LCCs) is believed to play a critical role in the cascade of biochemical events leading to neuron death in these pathophysiological conditions. So far, the mechanism of the interaction of IL-1beta and LCCs in the initiation and progression of these diseases is unclear. In this study, we investigate systemically the effects of IL-1beta on the LCCs current, which are believed to be implicated in the cascade of biochemical events leading to neuron death in neuropathological conditions. Using patch clamp, we observe that IL-1beta treatment (10 ng/ml, 24 h) suppresses LCC currents by approximately 38%, which made up half of the whole-cell Ca2+ current determined by nifedipine. IL-1beta does not alter the characteristics of single LCC including current amplitude, open probability, and conductance, but decreases the number of the functioning channel by 40%. Moreover, immunoblot assay exhibits that IL-1beta reduces the expression of LCC proteins by 38 approximately 42% in both whole neuron and plasma membrane fraction, and demonstrates that IL-1beta downregulates the LCC activity via the reduction of LCC density. According to early research pretreatments longer than 12 h may play a crucial role in the neuroprotective effects of IL-1beta, our findings may establish an explanation for the protective effects of this interleukin on neurons in the late stage of injury, and could raise a new issue to clinical treatment for insults to brain.