Apolipoprotein E Isoforms Increase Intracellular Ca2+ Differentially Through a ω-Agatoxin IVa-Sensitive Ca2+-Channel |
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Authors: | W. Mü ller,V. Meske,K. Berlin,H. Scharnagl,W. Mä rz,T.G. Ohm |
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Affiliation: | Institut für Physiologie der Charité, Tucholskystr. 2, D-10117 Berlin, Germany;Institut für Anatomie, D-10098 Berlin, Germany;Abteilung Klinische Chemie, Universität Freiburg, D-79106 Freiburg, Germany |
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Abstract: | Apolipoprotein E (apoE) is the major apolipoprotein in the brain and is known for its important role in plasticity and neurodegeneration. We show that apoE dose-dependently increases intracellular free Ca2+ in rat hippocampal astrocytes and neurons. This effect varies with isoforms in the order E4>E3>E2. It is insensitive to blockade of action potentials by tetrodotoxin or inhibition of binding of apoE by heparinase, by the LRP ligand lactoferrin and by low density lipoprotein. ApoE evoked Ca2+-increases are blocked in zero [Ca]o and by the Ca-channel antagonists nickel and ω-Agatoxin-IVa but not by nifedipine and ω-Conotoxin-GVIa, demonstrating an isoform-specific activation of P/Q type Ca2+-channels. This novel mechanism is discussed with respect to Alzheimer's disease, that is linked for most cases to the apoE ε-allelic variation (ε4 > ε3 > ε2). |
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