Regulation of intracellular Ca2+ concentration by interleukin-1beta in rat cortical synaptosomes: an age-related...

The pro-inflammatory cytokine interleukin-1beta (IL-1beta) is released by cells during injury and stress, and increased neuronal expression of IL-1beta is a feature of age-related neurodegeneration. We have recently reported that IL-1beta has a biphasic effect on the K+-induced rise in intracellular Ca2+ concentration ([Ca2+]i) in cortical synaptosomes, exerting an inhibitory effect on the K+-induced rise in [Ca2+]i at lower (3.5 ng/mL) concentrations and a stimulatory effect on the K+-induced rise in [Ca2+]i at higher (100 ng/mL) concentrations. In the present study, we observed that the K+-induced rise in [Ca2+]i was inhibited to a similar extent by the lower concentration of IL-1beta in cortical synaptosomes prepared from young (3-month-old), middle-aged (12-month-old) and aged (24-month-old) rats. In contrast, cortical synaptosomes prepared from the aged rats exhibited an increased susceptibility to the higher concentration of IL-1beta, resulting in a marked elevation in [Ca2+]i. We propose that the age-related increase in neuronal concentration of IL-1beta promotes a dramatic elevation in [Ca2+]i following membrane depolarization, thereby altering Ca2+ homeostasis and exacerbating neuronal vulnerability to excitotoxicity.