Monte Carlo simulation of 3-D buffered Ca2+ neuroendocrine cells

Buffered Ca2+ diffusion in the cytosol of neuroendocrine cells is a plausib le explanation for the slowness and latency in the secretion of hormones. W e have developed a Monte Carlo simulation to treat the problem of 3-D diffu sion and kinetic reactions of ions and buffers. The 3-D diffusion is modele d as a random walk process that follows the path of each ion and buffer mol ecule, combined locally with a stochastic treatment of the first-order kine tic reactions involved. Such modeling is able to predict [Ca2+] and buffer concentration time courses regardless of how low the calcium influx is, and it is therefore a convenient method for dealing with physiological calcium currents and concentrations. We study the effects of the diffusional and k inetic parameters of the model on the concentration time courses as well as on the local equilibrium of buffers with calcium. An in-mobile and fast en dogenous buffer as described by Klingauf and Neher (1997, Biophys. J. 72:67 4-690) was able to reach local equilibrium with calcium; however, the exoge nous buffers considered are displaced drastically from equilibrium at the s tart of the calcium pulse, particularly below the pores. The versatility of the method also allows the effect of different arrangements of calcium cha nnels on submembrane gradients to be studied, including random distribution of calcium channels and channel clusters. The simulation shows how the par ticular distribution of channels or clusters can be of relevance for secret ion in the case where the distribution of release granules is correlated wi th the channels or clusters.