Figure 3.

Kinetic schemes accounting for the observed InsP₃R channel response latencies. (A) A qualitative model stipulating distinct high-affinity inhibitory and activating Ca²⁺ sites in each InsP₃R channel. C and O represent closed inactive and active channel conformations. Channel conformations with different ligand binding states are explicitly shown in the scheme by superscript and subscript numbers in different colours: number of occupied high-affinity Ca²⁺ inhibitory sites in red, occupied high-affinity activating Ca²⁺ sites in black and occupied InsP₃ sites in green (as indicated by the key at the top right). Ligand binding and dissociation are indicated by arrows: InsP₃ binding in green, Ca²⁺ binding to inhibitory sites in red and Ca²⁺ binding to activating sites in black. Yellow arrows represent conformation changes. Because the channel is a tetrameric unit, more than one Ca²⁺ can bind to either the activating or inhibitory sites. Those ligand-binding states are not shown in the scheme for clarity. Multiple InsP₃ binding to the channel (dashed lines) is shown to demonstrate that the scheme can accommodate branched Markov chains. (B) A qualitative allosteric model stipulating only one kind of high-affinity Ca²⁺ site in an InsP₃R channel. Occupation of the InsP₃ binding sites causes the channel to adopt the C and D conformations instead of the A and B conformations, so that Ca²⁺ binding to the high-affinity Ca²⁺ site becomes activating instead of inhibitory. Unlike (A), only conformation changes are shown in this kinetic scheme. InsP₃ and Ca²⁺ binding to the channel, and the ligand-binding state of the channel conformations are omitted for clarity.