Multi-scale data-driven modeling and observation of calcium puffs.

Abstract:

:The spatiotemporal dynamics of elementary Ca(2+) release events, such as "blips" and "puffs" shapes the hierarchal Ca(2+) signaling in many cell types. Despite being the building blocks of Ca(2+) patterning, the mechanism responsible for the observed properties of puffs, especially their termination is incompletely understood. In this paper, we employ a data-driven approach to gain insights into the complex dynamics of blips and puffs. We use a model of inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) derived directly from single channel patch clamp data taken at 10 μM concentration of IP(3) to simulate calcium puffs. We first reproduce recent observations regarding puffs and blips and then investigate the mechanism of puff termination. Our model suggests that during a puff, IP(3)R s proceed around a loop through kinetic states from "rest" to "open" to "inhibited" and back to "rest". A puff terminates because of self-inhibition. Based on our simulations, we rule out the endoplasmic reticulum (ER) Ca(2+) depletion as a possible cause for puff termination. The data-driven approach also enables us to estimate the current through a single IP(3)R and the peak Ca(2+) concentration near the channel pore.

journal_name

Cell Calcium

journal_title

Cell calcium

authors

Ullah G,Parker I,Mak DO,Pearson JE

doi

10.1016/j.ceca.2012.04.018

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

152-60

issue

2

eissn

0143-4160

issn

1532-1991

pii

S0143-4160(12)00092-9

journal_volume

52

pub_type

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