Abstract
We examine closed-form approximations for the equilibrium Ca(2+) and buffer concentrations near a point Ca(2+) source representing a Ca(2+) channel, in the presence of a mobile buffer with two Ca(2+) binding sites activated sequentially and possessing distinct binding affinities and kinetics. This allows us to model the impact on Ca(2+) nanodomains of realistic endogenous Ca(2+) buffers characterized by cooperative Ca(2+) 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(2+) buffers with a single Ca(2+) 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(2+) 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.