Comparison of gating dynamics of different IP₃R channels with immune algorithm searching for channel parameter...

The gating properties of the inositol 1, 4, 5-trisphosphate (IP₃) receptor (IP₃R) are determined by the binding and unbinding capability of Ca²⁺ ions and IP₃ messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP₃R (Oo-IP₃R1), type-3 IP₃R (Oo-IP₃R3) and Spodoptera frugiperda IP₃R (Sf-IP₃R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP₃Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model. By comparing the fitting parameter distributions of three IP₃Rs, we suggest that the three types of IP₃Rs have the similar open sensitivity in responding to IP₃. The Oo-IP₃R3 channel is easy to open in responding to low Ca²⁺ concentration, while Sf-IP₃R channel is easily inhibited in responding to high Ca²⁺ concentration. We also show that the IP₃ binding rate is not a sensitive parameter for stationary gating dynamics for three IP₃Rs, but the inhibitory Ca²⁺ binding/unbinding rates are sensitive parameters for gating dynamics for both Oo-IP₃R1 and Oo-IP₃R3 channels. Such differences may be important in generating the spatially and temporally complex Ca²⁺ oscillations in cells. Our study also demonstrates that the immune algorithm can be applied for model parameter searching in biological systems.