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. 2006 Apr 5;8(4):641–653. doi: 10.1111/j.1750-3639.1998.tb00190.x

Apolipoprotein E Isoforms Increase Intracellular Ca2+ Differentially Through a ω‐Agatoxin IVa‐Sensitive Ca2+‐Channel

W Müller 1,✉, V Meske 2, K Berlin 1, H Scharnagl 3, W März 3, TG Ohm 2
PMCID: PMC8098222  PMID: 9804373

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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W. Müller and V.Meske contributed equally to this study.

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