Modeling the neuroprotective role of enhanced astrocyte mitochondrial metabolism during stroke

Casey O. Diekman, Christopher P. Fall, James D. Lechleiter, David Terman

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

A mathematical model that integrates the dynamics of cell membrane potential, ion homeostasis, cell volume, mitochondrial ATP production, mitochondrial and endoplasmic reticulum Ca2+ handling, IP3 production, and GTP-binding protein-coupled receptor signaling was developed. Simulations with this model support recent experimental data showing a protective effect of stimulating an astrocytic GTP-binding protein-coupled receptor (P2Y1Rs) following cerebral ischemic stroke. The model was analyzed to better understand the mathematical behavior of the equations and to provide insights into the underlying biological data. This approach yielded explicit formulas determining how changes in IP3-mediated Ca 2+ release, under varying conditions of oxygen and the energy substrate pyruvate, affected mitochondrial ATP production, and was utilized to predict rate-limiting variables in P2Y1R-enhanced astrocyte protection after cerebral ischemic stroke.

Original languageEnglish (US)
Pages (from-to)1752-1763
Number of pages12
JournalBiophysical Journal
Volume104
Issue number8
DOIs
StatePublished - Apr 16 2013

ASJC Scopus subject areas

  • Biophysics

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