Biomedical Engineering Reference
In-Depth Information
models in this area. Magnus and Keizer [30] proposed a model for mitochondrial
calcium dynamics that included the processes that generated the membrane poten-
tial across the inner mitochondrial membrane since this is responsible for powering
the calcium uniporter. This is a comprehensive model and has been incorporated
into the pancreatic c cell [31, 32]. One of the key predictions of the model is that
when cytosolic calcium rises, it increases mitochondrial calcium, which reduces the
mitochondrial membrane potential resulting in decreased ATP production. More re-
cently, this model has been incorporated by Fall and Keizer [16] into a model of
calcium signaling to show how mitochondrial calcium dynamics affected calcium
signaling. Depending on the parameters chosen, the DeYoung-Keizer model [13]
can give oscillatory or bi-stable calcium dynamics. The addition of the mitochon-
drial model to a DeYoung-Keizer model [16] tuned to give bi-stable behavior results
in a model with oscillatory calcium dynamics. Furthermore, the model predicts that
increasing metabolism slows the frequency of calcium oscillations consistent with
experiments [26].
This latter finding was also modeled by Falcke and co-workers [15]. They added
a simplified model of uniporter and
Na
+
−
Ca
2
+
exchange to the Tang and Othmer
model [51] for calcium signaling. They simulated energization of the mitochondria
by increasing the maximal calcium uptake rate for the uniporter.
Finally, a recent model for the effects of mitochondrial calcium dynamics on cel-
lular calcium signaling was developed for sympathetic neurons by Colegrove and co-
workers [10]. Once again, simple formulations for mitochondrial uptake and release
were implemented into a model for neuronal calcium dynamics. The model sug-
gested that the mitochondria will accumulate calcium even under low amplitude fluc-
tuations of cytosolic calcium and that the impact of mitochondrial calcium dynamics
on cytosolic calcium is influenced greatly by non-mitochondrial calcium handling
mechanisms. Furthermore, the model predicted that the buffering and non-buffering
modes of mitochondrial calcium dynamics correspond to two different calcium sig-
naling regimes.
3.3
Special calcium signaling for neurons
Thus far, the mechanisms of calcium signaling described are general and can be ap-
plied to many different cell types. Neurons are specialized cells that are varied in
their function and morphology. This results in many calcium handling features de-
signed to perform specific functions. Although some of them functions might be
specific to neurons, the constructs to describe these are often found in other cells.
These features occur in different parts of the neuron, namely, the soma, nerve ter-
minal, dendrites and dendritic spines, and axon. In the next section, three specific
calcium signaling mechanisms will be discussed: local calcium signaling, the con-
trol of gene expression by calcium, and cross-talk between channels mediated by
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