Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity
CICR is based on the nonlinear open probability of IP3R. (a) Scheme of the DeYoung-Keizer model for a single subunit. A subunit is active, if IP3 (I) is bound and Ca2+ (C) is only bound to the activating site, that is, in state . A channel opens if at least 3 of its 4 subunits are active. Open IP3Rs release Ca2+ that can diffuse to other IP3R clusters and activate the channels there as well, eventually leading to cell wide Ca2+ release and generating a spike. From the cytosol Ca2+ is pumped back into the ER by SERCA that decreases diffusion. (b) From the Markov chain model of a single subunit the non-Markovian stationary open probability of a channel can be calculated in dependence on Ca2+ and IP3 concentration .
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