Enhancement of 45Ca2+ influx and voltage-dependent Ca2+ channel activity by β-amyloid-(1-40) in rat cortical synaptosomes and cultured cortical neurons -: Modulation by the proinflammatory cytokine interleukin-1β

beta-Amyloid protein is thought to underlie the neurodegeneration associated with Alzheimer's disease by inducing Ca2+-dependent apoptosis, Elevated neuronal expression of the proinflammatory cytokine interleukin-1 beta is an additional feature of neurodegeneration, and in this study we demonstrate that interleukin-1 beta modulates the effects of beta-amyloid on Ca2+ homeostasis in the rat cortex. beta-Amyloid-(1-40) (1 mu M) caused a significant increase in Ca-45(2+) influx into rat cortical synaptosomes via activation of L- and N-type voltage-dependent Ca2+ channels and also increased the amplitude of N- and P-type Ca2+ channel currents recorded from cultured cortical neurons. In contrast, interleukin-1 beta (5 ng/ml) reduced the Ca-45(2+) influx into cortical synaptosomes and inhibited Ca2+ channel activity in cultured cortical neurons. Furthermore, the stimulatory effects of beta-amyloid protein on Ca2+ influx were blocked following exposure to interleukin-1 beta, suggesting that interleukin-1 beta may govern neuronal responses to beta-amyloid by regulating Ca2+ homeostasis.