A General Analysis of Single IP3 Receptors Modulated by Cytosolic Ca2+ and IP3

In this report, we remove the constraint of detailed balance and give a general discussion of the modulation of cytosolic Ca2+ and IP3 on the IP3R channel. By introducing the circulation decomposition theorem in stochastic process, the gating mechanism of single IP3R is neatly analyzed. Some remarkable differences are found to distinguish between equilibrium and non-equilibrium dynamics. Evidence is given to show that detailed balance is violated to some extent in the IP3R channel. Comparison of surface fittings between equilibrium and non-equilibrium models reveals that the latter model excels evidently. It is emphasized that these interesting phenomena in the non-equilibrium dynamics, present a more comprehensive view of the channel behavior.