Stationary Ca2+ nanodomains in the presence of buffers with two binding sites.

We examine closed-form approximations for the equilibrium Ca2+ and buffer concentrations near a point Ca2+ source representing a Ca2+ channel, in the presence of a mobile buffer with two Ca2+ binding sites activated sequentially and possessing distinct binding affinities and kinetics. This allows us to model the impact on Ca2+ nanodomains of realistic endogenous Ca2+ buffers characterized by cooperative Ca2+ binding, such as calretinin. The approximations we present involve a combination or rational and exponential functions, whose parameters are constrained using the series interpolation method that we recently introduced for the case of simpler Ca2+ buffers with a single Ca2+ binding site. We conduct extensive parameter sensitivity analysis and show that the obtained closed-form approximations achieve reasonable qualitative accuracy for a wide range of buffer's Ca2+ binding properties and other relevant model parameters. In particular, the accuracy of the derived approximants exceeds that of the rapid buffering approximation in large portions of the relevant parameter space.