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

We examine closed-form approximations for the equilibrium Ca and buffer concentrations near a point Ca source representing a Ca channel, in the presence of a mobile buffer with two Ca binding sites activated sequentially and possessing distinct binding affinities and kinetics. This allows us to model the impact on Ca nanodomains of realistic endogenous Ca buffers characterized by cooperative Ca 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 Ca buffers with a single Ca 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 Ca 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.