Extension of Rapid Buffering Approximation to Ca2+ Buffers with Two Binding Sites

Document Type

Article

Publication Date

3-13-2018

Abstract

Fundamental cell processes such as synaptic neurotransmitter release, endocrine hormone secretion, and myocyte contraction are controlled by highly localized calcium (Ca2+) signals resulting from brief openings of trans-membrane Ca2+ channels. On short temporal and spatial scales, the corresponding local Ca2+ nanodomains formed in the vicinity of a single or several open Ca2+ channels can be effectively approximated by quasi-stationary solutions. The rapid buffering approximation (RBA) is one of the most powerful of such approximations, and is based on the assumption of instantaneous equilibration of the bimolecular Ca2+ buffering reaction, combined with the conservation condition for the total Ca2+ and buffer molecule numbers. Previously, RBA has been generalized to an arbitrary arrangement of Ca2+ channels on a flat membrane, in the presence of any number of simple Ca2+ buffers with one-to-one Ca2+ binding stoichiometry. However, many biological buffers have multiple binding sites. For example, buffers and sensors phylogenetically related to calmodulin consist of two Ca2+-binding domains (lobes), with each domain binding two Ca2+ ions in a cooperative manner. Here we consider an extension of RBA to such buffers with two interdependent Ca2+ binding sites. We show that in the presence of such buffers, RBA solution is given by the solution to a cubic equation, analogous to the quadratic equation describing RBA in the case of a simple, one-to-one Ca2+ buffer. We examine in detail the dependence of RBA accuracy on buffering parameters, to reveal conditions under which RBA provides sufficient precision.

Identifier

85043515872 (Scopus)

Publication Title

Biophysical Journal

External Full Text Location

https://doi.org/10.1016/j.bpj.2018.01.019

e-ISSN

15420086

ISSN

00063495

PubMed ID

29539405

First Page

1204

Last Page

1215

Issue

5

Volume

114

Grant

DMS-1517085

Fund Ref

National Science Foundation

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