TY - JOUR
T1 - Modeling the neuroprotective role of enhanced astrocyte mitochondrial metabolism during stroke
AU - Diekman, Casey O.
AU - Fall, Christopher P.
AU - Lechleiter, James D.
AU - Terman, David
N1 - Funding Information:
This research has been supported by the National Institutes of Health under National Institute for Aging grant No. AG29461 (to J.D.L.) and National Institute of Mental Health grant No. MH64611 (to C.P.F.), and by the National Science Foundation under Division of Mathematical Sciences grants No. 0718558 (to C.P.F.), No. 1022627 (to D.T.), and No. 0931642 (to the Mathematical Biosciences Institute).
Funding Information:
The authors thank the Mathematical Biosciences Institute at The Ohio State University and the National Science Foundation supported Computational Cell Biology course at Cold Spring Harbor Laboratory for facilitating our collaboration.
PY - 2013/4/16
Y1 - 2013/4/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bpj.2013.02.025
DO - 10.1016/j.bpj.2013.02.025
M3 - Article
C2 - 23601322
AN - SCOPUS:84876378046
SN - 0006-3495
VL - 104
SP - 1752
EP - 1763
JO - Biophysical Journal
JF - Biophysical Journal
IS - 8
ER -