Gregory D. Smith
Modeling the stochastic dynamics of localized calcium elevations
and whole-cell calcium responses
Abstract
Localized Ca elevations known as Ca puffs and sparks are
cellular signals that arise from the cooperative activity of clusters of
inositol 1,4,5-trisphosphate receptors and ryanodine receptors clustered
at Ca release sites on the surface of the endoplasmic reticulum or
sarcoplasmic reticulum. When Markov chain models of intracellular Ca
regulated Ca channels are coupled via a mathematical representation of a
Ca microdomain, simulated Ca release sites may exhibit the phenomenon of
stochastic Ca excitability where the IP3Rs or RyRs open and close in a
concerted fashion. Such mathematical models provide insight into the
relationship between single-channel kinetics and the statistics of
puff/spark duration, and clarify the role of stochastic attrition, Ca
inactivation, luminal depletion, and allosteric interactions in the
dynamics of puff/spark termination. The stochastic dynamics of local Ca is
an important aspect of excitation-contraction coupling in cardiac
myocytes, where sarcoplasmic reticulum Ca-induced Ca release is locally
controlled by trigger Ca influx via L-type channels of the plasma
membrane. A recently developed whole cell modeling approach is able to
avoid the computationally demanding task of resolving spatial aspects of
global Ca signaling by using probability densities and associated moment
equations to representing heterogeneous local Ca signals in a population
of Ca release units.
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