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Apolipoprotein E isoforms increase intracellular Ca2+ differentially through a omega-agatoxin IVa-sensitive
1Institut für Physiologie der Charité, Berlin, Germany. mueller@rz.charite.hu-berlin.de
Brain Pathology (Zurich, Switzerland)
|November 6, 1998
Summary
Apolipoprotein E (apoE) increases intracellular calcium in brain cells, with the E4 isoform having the strongest effect. This occurs via P/Q type calcium channels, a finding relevant to Alzheimer's disease.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Apolipoprotein E (apoE) is crucial for brain plasticity and neurodegeneration.
- The apoE epsilon 4 allele is a major genetic risk factor for Alzheimer's disease.
Purpose of the Study:
- To investigate the effect of apoE on intracellular calcium levels in rat hippocampal astrocytes and neurons.
- To determine if apoE's effect on calcium is isoform-dependent and the underlying mechanism.
Main Methods:
- Primary cultures of rat hippocampal astrocytes and neurons were used.
- Intracellular free Ca2+ was measured following apoE application.
- Pharmacological agents were used to block specific calcium channels and apoE binding.
Main Results:
- Apolipoprotein E dose-dependently increased intracellular free Ca2+ in a manner dependent on apoE isoforms (E4 > E3 > E2).
- The apoE-evoked Ca2+ increase was blocked by zero extracellular Ca2+ and specific Ca2+ channel antagonists (Ni2+, omega-Agatoxin-IVa).
- This indicates activation of P/Q type Ca2+-channels, independent of action potentials or known apoE binding pathways.
Conclusions:
- Apolipoprotein E isoforms differentially regulate intracellular calcium via P/Q type calcium channels in neurons and astrocytes.
- This novel mechanism provides insight into the role of apoE in neurobiology and its connection to Alzheimer's disease risk.