Enhancement of (45)Ca(2+) influx and voltage-dependent Ca(2+) channel activity by beta-amyloid-(1-40) in rat cortical synaptosomes and cultured cortical neurons. Modulation by the proinflammatory cytokine interleukin-1beta.
Beta-amyloid protein is thought to underlie the neurodegeneration associated with Alzheimer's disease by inducing Ca(2+)-dependent apoptosis. Elevated neuronal expression of the proinflammatory cytokine interleukin-1beta is an additional feature of neurodegeneration, and in this study we demonstrate that interleukin-1beta modulates the effects of beta-amyloid on Ca(2+) homeostasis in the rat cortex. beta-Amyloid-(1-40) (1 microM) caused a significant increase in (45)Ca(2+) influx into rat cortical synaptosomes via activation of L- and N-type voltage-dependent Ca(2+) channels and also increased the amplitude of N- and P-type Ca(2+) channel currents recorded from cultured cortical neurons. In contrast, interleukin-1beta (5 ng/ml) reduced the (45)Ca(2+) influx into cortical synaptosomes and inhibited Ca(2+) channel activity in cultured cortical neurons. Furthermore, the stimulatory effects of beta-amyloid protein on Ca(2+) influx were blocked following exposure to interleukin-1beta, suggesting that interleukin-1beta may govern neuronal responses to beta-amyloid by regulating Ca(2+) homeostasis.
MacManus
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A
Department of Physiology, Trinity College, Dublin 2, Ireland.
Ramsden
M
M
Murray
M
M
Henderson
Z
Z
Pearson
H A
HA
Campbell
V A
VA
D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis; D007375:Interleukin-1 / Q000502:physiology*; D015640:Ion Channel Gating; D017136:Ion Transport; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D020746:Calcium Channels, L-Type; D007375:Interleukin-1; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D002118:Calcium