TABLE III The RYR2 Activation Associated... | Rockefeller University Press

TABLE III

The RYR2 Activation Associated with Various Combinations of Functional States among Its Four Subunits

Subunit stoichiometry	i	Opening rate constant, R_O	Closing rate constant, R_C	Probability of stoichiometry P_S	Probability of stoichiometry given closed, P_SC	Probability of stoichiometry given open, P_SO
4L 0H	1	α	δ	\(P_{L}^{4}\)	\(P_{L}^{4}{\times}N/(1{+}{\alpha}/{\delta})\)	\(P_{L}^{4}{\times}M/(1{+}{\delta}/{\alpha})\)
3L 1H	2	β	δ	\(4P_{L}^{3}P_{H}\)	\(4P_{L}^{3}P_{H}{\times}N/(1{+}{\beta}/{\delta})\)	\(4P_{L}^{3}P_{H}{\times}M/(1{+}{\delta}/{\beta})\)
2L 2H	3	β	δ	\(6P_{L}^{2}P_{H}^{2}\)	\(6P_{L}^{2}P_{H}^{2}{\times}N/(1{+}{\beta}/{\delta})\)	\(6P_{L}^{2}P_{H}^{2}{\times}M/(1{+}{\delta}/{\beta})\)
1L 3H	4	γ	δ	\(4P_{L}P_{H}^{3}\)	\(4P_{L}P_{H}^{3}{\times}N/(1{+}{\gamma}/{\delta})\)	\(4P_{L}P_{H}^{3}{\times}M/(1{+}{\delta}/{\gamma})\)
0L 4H	5	γ	ε	\(P_{H}^{4}\)	\(P_{H}^{4}{\times}N/(1{+}{\gamma}/{\epsilon})\)	\(P_{H}^{4}{\times}M/(1{+}{\epsilon}/{\gamma})\)
3L 0H 1C	6	α	δ	\(4P_{L}^{3}P_{C}\)	\(4P_{L}^{3}P_{C}{\times}N/(1{+}{\alpha}/{\delta})\)	\(4P_{L}^{3}P_{C}{\times}N/(1{+}{\alpha}/{\delta})\)
2L 1H 1C	7	β	δ	\(12P_{L}^{2}P_{H}P_{C}\)	\(12P_{L}^{2}P_{H}P_{C}{\times}N/(1{+}{\beta}/{\delta})\)	\(12P_{L}^{2}P_{H}P_{C}{\times}M/(1{+}{\delta}/{\beta})\)
1L 2H 1C	8	β	δ	\(12P_{L}P_{H}^{2}P_{C}\)	\(12P_{L}P_{H}^{2}P_{C}{\times}N/(1{+}{\beta}/{\delta})\)	\(12P_{L}P_{H}^{2}P_{C}{\times}M/(1{+}{\delta}/{\beta})\)
0L 3H 1C	9	γ	δ	\(4P_{H}^{3}P_{C}\)	\(4P_{H}^{3}P_{C}{\times}N/(1{+}{\gamma}/{\delta})\)	\(4P_{H}^{3}P_{C}{\times}M/(1{+}{\delta}/{\gamma})\)
others	10	0	δ	\(1{-}{{\sum}_{i{=}1}^{9}}P_{S}\)	\(\left(1{-}{{\sum}_{i{=}1}^{9}}P_{S}\right){\times}N\)	0

Subunit stoichiometry	i	Opening rate constant, R_O	Closing rate constant, R_C	Probability of stoichiometry P_S	Probability of stoichiometry given closed, P_SC	Probability of stoichiometry given open, P_SO
4L 0H	1	α	δ	\(P_{L}^{4}\)	\(P_{L}^{4}{\times}N/(1{+}{\alpha}/{\delta})\)	\(P_{L}^{4}{\times}M/(1{+}{\delta}/{\alpha})\)
3L 1H	2	β	δ	\(4P_{L}^{3}P_{H}\)	\(4P_{L}^{3}P_{H}{\times}N/(1{+}{\beta}/{\delta})\)	\(4P_{L}^{3}P_{H}{\times}M/(1{+}{\delta}/{\beta})\)
2L 2H	3	β	δ	\(6P_{L}^{2}P_{H}^{2}\)	\(6P_{L}^{2}P_{H}^{2}{\times}N/(1{+}{\beta}/{\delta})\)	\(6P_{L}^{2}P_{H}^{2}{\times}M/(1{+}{\delta}/{\beta})\)
1L 3H	4	γ	δ	\(4P_{L}P_{H}^{3}\)	\(4P_{L}P_{H}^{3}{\times}N/(1{+}{\gamma}/{\delta})\)	\(4P_{L}P_{H}^{3}{\times}M/(1{+}{\delta}/{\gamma})\)
0L 4H	5	γ	ε	\(P_{H}^{4}\)	\(P_{H}^{4}{\times}N/(1{+}{\gamma}/{\epsilon})\)	\(P_{H}^{4}{\times}M/(1{+}{\epsilon}/{\gamma})\)
3L 0H 1C	6	α	δ	\(4P_{L}^{3}P_{C}\)	\(4P_{L}^{3}P_{C}{\times}N/(1{+}{\alpha}/{\delta})\)	\(4P_{L}^{3}P_{C}{\times}N/(1{+}{\alpha}/{\delta})\)
2L 1H 1C	7	β	δ	\(12P_{L}^{2}P_{H}P_{C}\)	\(12P_{L}^{2}P_{H}P_{C}{\times}N/(1{+}{\beta}/{\delta})\)	\(12P_{L}^{2}P_{H}P_{C}{\times}M/(1{+}{\delta}/{\beta})\)
1L 2H 1C	8	β	δ	\(12P_{L}P_{H}^{2}P_{C}\)	\(12P_{L}P_{H}^{2}P_{C}{\times}N/(1{+}{\beta}/{\delta})\)	\(12P_{L}P_{H}^{2}P_{C}{\times}M/(1{+}{\delta}/{\beta})\)
0L 3H 1C	9	γ	δ	\(4P_{H}^{3}P_{C}\)	\(4P_{H}^{3}P_{C}{\times}N/(1{+}{\gamma}/{\delta})\)	\(4P_{H}^{3}P_{C}{\times}M/(1{+}{\delta}/{\gamma})\)
others	10	0	δ	\(1{-}{{\sum}_{i{=}1}^{9}}P_{S}\)	\(\left(1{-}{{\sum}_{i{=}1}^{9}}P_{S}\right){\times}N\)	0

The kinetic scheme for channel gating is shown in Fig. 10 (scheme 1). States C, L, and H depend on Ca²⁺ and Mg²⁺ binding to the A- and L-sites, which is described in Table II A. Subunit stoichiometries (i = 1–5) are the combinations of four active subunits that produce channel openings and stoichiometries 6–9 are combinations of three active subunits. Other stoichiometries are deemed not to produce channel openings. Associated with each stoichiometry is the channel opening and closing rate constants, the probability that the channel has that stoichiometry, and the probabilities of the channel open and closed states. Values for the rate constants are given in Table V. The values M and N are normalizing factors:

\[N{=}1\left/{{\sum}_{i{=}1}^{10}}P_{SCi}\right.,\]

\[M{=}1\left/{{\sum}_{i{=}1}^{10}}P_{SOi}\right..\]

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