Robustness of calcium activation to spatial localization of IP3R and RyR as revealed by semi-stochastic simulation

Summary form only given. Inositol 1,4,5-trisphosphate and ryanodine receptors (IP3R and RyR) play important roles in Ca²⁺ signaling leading a variety of spatio-temporal patterns that control vital cell functions. Currently, signaling through these Ca²⁺ receptors/channels is primarily modeled either using stochastic approaches to a single receptor activation or deterministic equations describing the bulk properties of multiple channels. Both approaches fail to account for possible spatial inhomogeneities of the channel distribution in endoplasmic or sarcoplasmic reticula. Here I present a generic model of IP3R and RyR stochastically distributed in 2D plane. The model predicts that the biphasic dependency of the channel opening probability on Ca²⁺ concentration observed for both receptor types serves to ensure robustness of Ca²⁺ responses initiated by Ca²⁺ upregulation or other stimuli, including IP3 and ryanodine. In particular I show that calcium response is robust to local variations in channel density and partial inhibition of channel function following the response initiation. Conditions for generation of spatial waves of activity and variations in their shape are also discussed. The model presents another perspective on understanding the opening characteristics of IP3R and RyR.