Quantifying the uncertainty of spontaneous Ca 2+ oscillations in astrocytes: Particulars of Alzheimer's disease

J. Riera, R. Hatanaka, T. Uchida, T. Ozaki, R. Kawashima

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)554-564
Number of pages11
JournalBiophysical Journal
Volume101
Issue number3
DOIs
Publication statusPublished - 2011 Aug 3

ASJC Scopus subject areas

  • Biophysics

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