Regulation of intracellular Ca2+ concentration by interleukin-1beta in rat cortical synaptosomes: an age-related study.
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.
Campbell
V A
VA
Department of Physiology, Trinity College, Dublin 2, Ireland. vacmpbll@mail.tcd.ie
Segurado
R
R
Lynch
M A
MA
D000375:Aging / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase; D013574:Synaptosomes / Q000502:physiology*
D007375:Interleukin-1; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium