Stochastic simulation of calcium microdomains in the vicinity of an L-type calcium channel |
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Authors: | Frederic von Wegner R H A Fink |
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Institution: | (1) Medical Biophysics, Institute for Physiology and Pathophysiology, University of Heidelberg, INF 326, 69120 Heidelberg, Germany |
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Abstract: | We study numerically the local dynamics of the intracellular calcium concentration in the vicinity of a voltage- and calcium-dependent
plasma membrane L-type calcium channel. To account for the low number of Ca2+ ions and buffer molecules present in sub-femtoliter volumes, we use an exact stochastic simulation algorithm including diffusion.
We present a novel, unified simulation method that implements reaction-diffusion events of Ca2+ ions and buffer molecules, stochastic ion channel gating and channel conductance as a multivariate Markov process. For fixed-voltage
dynamics, e.g. under voltage-clamp conditions, it is shown that voltage-sensitive channel-gating steps can be incorporated
exactly. We compare multi- and single-voxel geometries and show that the single-voxel approach leads to almost identical first-
and second-order moments, at much lower computation time. Numerical examples illustrate the variability in local Ca2+ fluctuations as induced by bursts of channel openings in response to membrane depolarisations. Finally, by introducing calmodulin
as a link, it is shown how this variability is passed on to downstream signalling pathways. The method may prove useful to
study calcium microdomains and calcium-regulated processes triggered by membrane depolarisations as evoked by, e.g., viral
channel-forming proteins during virus-host cell interactions. |
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