Stochastic simulation of calcium microdomains in the vicinity of an L-type calcium channel.
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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
von Wegner
Frederic
F
Medical Biophysics, Institute for Physiology and Pathophysiology, University of Heidelberg, INF 326, 69120, Heidelberg, Germany. fwegner@physiologie.uni-heidelberg.de
Fink
R H A
RH
D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000737:chemistry*; D020746:Calcium Channels, L-Type / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry; D054884:Host-Pathogen Interactions; D006801:Humans; D007700:Kinetics; D008390:Markov Chains; D008564:Membrane Potentials; D056004:Molecular Dynamics Simulation; D015398:Signal Transduction; D013269:Stochastic Processes; D013997:Time Factors
D020746:Calcium Channels, L-Type; D002147:Calmodulin; D002118:Calcium