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ABSTRACT I model the behavior of intracellular Ca^sup 2+^ release with high buffer concentrations. The model uses a spatially discrete array of channel clusters. The channel subunit dynamics is a stochastic representation of the DeYoung-Keizer model. The calculations show that the concentration profile of fast buffer around an open channel is more localized than that of slow buffers. Slow buffers allow for release of larger amounts of Ca^sup 2+^ from the endoplasmic reticulum and hence bind more Ca^sup 2+^ than fast buffers with the same dissociation constant and concentration. I find oscillation-like behavior for high slow buffer concentration and low Ca^sup 2+^ content of the endoplasmic reticulum. High concentration of slow buffer leads to oscillation-like behavior by repetitive wave nucleation for high Ca^sup 2+^ content of the endoplasmic reticulum. Localization of Ca^sup 2+^ release by slow buffer, as used in experiments, can be reproduced by the modeling approach.
INTRODUCTION
Ca^sup 2+^ is used as a second messenger in cell signaling (Tsien and Tsien, 1990; Berridge et al., 1998). Many cells respond with oscillations of the cytosolic Ca^sup 2+^ concentration to a variety of stimuli (Toescu, 1995; Kummer et al., 2000; Schuster et al., 2001). The rise of the cytosolic Ca^sup 2+^ concentration is accomplished by influx through the plasma membrane and release of Ca^sup 2+^ from intracellular stores like the endoplasmic reticulum (ER) into the cytosol. Opening and closing of Ca^sup 2+^ channels on the ER membrane controls the release. Ca^sup 2+^ is pumped back from the cytosol into the ER by SERCATPases.
The state of channels changes stochastically. The transition probabilities between the states depend on binding of ligands to the channel. The ligands are Ca^sup 2+^ and IP^sub 3^ in the case of the IP^sub 3^ receptor channel IP^sub 3^R (Taylor, 1998; Patel et al., 1999). That stochastic behavior manifests itself as spontaneous release events called puffs and the termination of wave propagation by fluctuations (abortive waves) (Sun et al., 1998; Callamaras and Parker, 2000; Marchant and Parker, 2001; Thomas et al., 1999; Bootman et al. 1997).
Channels are spatially grouped in clusters (Parker and Yao, 1991; Sun et al., 1998; Thomas et al., 1998; Mak et al., 2000; Mak and Foskett, 1998). The clusters are arranged irregularly on the ER membrane...