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Modeling Ca2+ feedback on a single inositol 1,4,5-trisphosphate receptor and its modulation by Ca2+ buffers

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Modeling Ca2+ feedback on a single inositol 1,4,5-trisphosphate receptor and its modulation by Ca2+ buffers.htm (400bytes)
Date
2008-10
Author
Shuai, Jianwei
帅建伟
Pearson, John E.
Parker, Ian
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  • 物理技术-已发表论文 [4223]
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Abstract
The inositol 1,4,5-trisphosphate receptor/channel (IP3R) is a major regulator of intracellular Ca2+ signaling, and liberates Ca2+ ions from the endoplasmic reticulum in response to binding at cytosolic sites for both IP3 and Ca2+. Although the steady-state gating properties of the IP3R have been extensively studied and modeled under conditions of fixed [IP3] and [Ca2+], little is known about how Ca2+ flux through a channel may modulate the gating of that same channel by feedback onto activating and inhibitory Ca2+ binding sites. We thus simulated the dynamics of Ca2+ self-feedback on monomeric and tetrameric IP3R models. A major conclusion is that self-activation depends crucially on stationary cytosolic Ca2+ buffers that slow the collapse of the local [Ca2+] microdomain after closure. This promotes burst-like reopenings by the rebinding of Ca2+ to the activating site; whereas inhibitory actions are substantially independent of stationary buffers but are strongly dependent on the location of the inhibitory Ca2+ binding site on the IP3R in relation to the channel pore
Citation
Biophysical Journal [0006-3495],2008,95(8):3738-3752
URI
http://dx.doi.org/doi:10.1529/biophysj.108.137182
https://dspace.xmu.edu.cn/handle/2288/10182

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