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Quantifying the uncertainty of spontaneous Ca2+ oscillations in astrocytes: particulars of Alzheimer's disease.

Abstract
The quantification of spontaneous calcium (Ca(2+)) oscillations (SCOs) in astrocytes presents a challenge because of the large irregularities in the amplitudes, durations, and initiation times of the underlying events. In this article, we use a stochastic context to account for such SCO variability, which is based on previous models for cellular Ca(2+) signaling. First, we found that passive Ca(2+) influx from the extracellular space determine the basal concentration of this ion in the cytosol. Second, we demonstrated the feasibility of estimating both the inositol 1,4,5-trisphosphate (IP(3)) production levels and the average number of IP(3) receptor channels in the somatic clusters from epifluorescent Ca(2+) imaging through the combination of a filtering strategy and a maximum-likelihood criterion. We estimated these two biophysical parameters using data from wild-type adult mice and age-matched transgenic mice overexpressing the 695-amino-acid isoform of human Alzheimer β-amyloid precursor protein. We found that, together with an increase in the passive Ca(2+) influx, a significant reduction in the sensitivity of G protein-coupled receptors might lie beneath the abnormalities in the astrocytic Ca(2+) signaling, as was observed in rodent models of Alzheimer's disease. This study provides new, to our knowledge, indices for a quantitative analysis of SCOs in normal and pathological astrocytes.
AuthorsJ Riera, R Hatanaka, T Uchida, T Ozaki, R Kawashima
JournalBiophysical journal (Biophys J) Vol. 101 Issue 3 Pg. 554-64 (Aug 3 2011) ISSN: 1542-0086 [Electronic] United States
PMID21806923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Inositol 1,4,5-Trisphosphate Receptors
  • Inositol 1,4,5-Trisphosphate
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium
Topics
  • Alzheimer Disease (metabolism, pathology)
  • Animals
  • Astrocytes (metabolism, pathology)
  • Calcium (metabolism)
  • Calcium Signaling
  • Cell Line, Tumor
  • Cell Membrane (metabolism)
  • Cytosol (metabolism)
  • Endoplasmic Reticulum (metabolism)
  • Extracellular Space (metabolism)
  • Hippocampus (metabolism, pathology)
  • Humans
  • Inositol 1,4,5-Trisphosphate (biosynthesis, metabolism)
  • Inositol 1,4,5-Trisphosphate Receptors (metabolism)
  • Mice
  • Models, Biological
  • Molecular Imaging
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)
  • Uncertainty

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