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

Document Type

Article

Publication Date

5-18-2021

Abstract

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.

Identifier

85103720649 (Scopus)

Publication Title

Biophysical Journal

External Full Text Location

https://doi.org/10.1016/j.bpj.2021.03.015

e-ISSN

15420086

ISSN

00063495

PubMed ID

33771472

First Page

1942

Last Page

1956

Issue

10

Volume

120

Grant

DMS-1517085

Fund Ref

National Institutes of Health

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