11 research outputs found
G protein-coupled receptor-mediated calcium signaling in astrocytes
Astrocytes express a large variety of G~protein-coupled receptors (GPCRs)
which mediate the transduction of extracellular signals into intracellular
calcium responses. This transduction is provided by a complex network of
biochemical reactions which mobilizes a wealth of possible calcium-mobilizing
second messenger molecules. Inositol 1,4,5-trisphosphate is probably the best
known of these molecules whose enzymes for its production and degradation are
nonetheless calcium-dependent. We present a biophysical modeling approach based
on the assumption of Michaelis-Menten enzyme kinetics, to effectively describe
GPCR-mediated astrocytic calcium signals. Our model is then used to study
different mechanisms at play in stimulus encoding by shape and frequency of
calcium oscillations in astrocytes.Comment: 35 pages, 6 figures, 1 table, 3 appendices (book chapter
Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes
Recent years have witnessed an increasing interest in neuron-glia
communication. This interest stems from the realization that glia participates
in cognitive functions and information processing and is involved in many brain
disorders and neurodegenerative diseases. An important process in neuron-glia
communications is astrocyte encoding of synaptic information transfer: the
modulation of intracellular calcium dynamics in astrocytes in response to
synaptic activity. Here, we derive and investigate a concise mathematical model
for glutamate-induced astrocytic intracellular Ca2+ dynamics that captures the
essential biochemical features of the regulatory pathway of inositol
1,4,5-trisphosphate (IP3). Starting from the well-known two-state Li-Rinzel
model for calcium-induced-calcium release, we incorporate the regulation of the
IP3 production and phosphorylation. Doing so we extended it to a three-state
model (referred as the G-ChI model), that could account for Ca2+ oscillations
triggered by endogenous IP3 metabolism as well as by IP3 production by external
glutamate signals. Compared to previous similar models, our three-state models
include a more realistic description of the IP3 production and degradation
pathways, lumping together their essential nonlinearities within a concise
formulation. Using bifurcation analysis and time simulations, we demonstrate
the existence of new putative dynamical features. The cross-couplings between
IP3 and Ca2+ pathways endows the system with self-consistent oscillator
properties and favor mixed frequency-amplitude encoding modes over pure
amplitude modulation ones. These and additional results of our model are in
general agreement with available experimental data and may have important
implications on the role of astrocytes in the synaptic transfer of information.Comment: 42 pages, 16 figures, 1 table. Figure filenames mirror figure order
in the paper. Ending "S" in figure filenames stands for "Supplementary
Figure". This article was selected by the Faculty of 1000 Biology: "Genevieve
Dupont: Faculty of 1000 Biology, 4 Sep 2009" at
http://www.f1000biology.com/article/id/1163674/evaluatio