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Selected Publication:
Müller, W; Meske, V; Berlin, K; Scharnagl, H; März, W; Ohm, TG.
Apolipoprotein E isoforms increase intracellular Ca2+ differentially through a omega-agatoxin IVa-sensitive Ca2+-channel.
BRAIN PATHOL 1998 8: 641-653.
Doi: 10.1111/j.1750-3639.1998.tb00190.x
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- Co-authors Med Uni Graz
- März Winfried
- Scharnagl Hubert
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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 omega-Agatoxin-IVa but not by nifedipine and omega-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 epsilon-allelic variation (epsilon4 > epsilon3 > epsilon2).
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apolipoproteins E - pharmacology
- Astrocytes - drug effects
- Calcium - metabolism
- Calcium Channel Blockers - pharmacology
- Calcium Channels - drug effects
- Cells, Cultured - drug effects
- Hippocampus - cytology
- Homeostasis - drug effects
- Immunohistochemistry - drug effects
- Isomerism - drug effects
- Lipid Metabolism - drug effects
- Neurons - drug effects
- Rats - drug effects
- Rats, Wistar - drug effects
- Research Support, Non-U.S. Gov't - drug effects
- Spider Venoms - pharmacology
- omega-Agatoxin IVA - pharmacology