Table 4.

Values and sensitivities of the threshold for CaOSS to the main conductances of the reduced model

	CaTot			CaTot Sensitivities
Model	Original, fmol	Threshold, fmol	Ratio of threshold to original	kRyR	kSERCA	kSSdiff
Iyer07*	1.34	2.76	2.06	−0.185‡	0.024	0.162
Fink08*	13.23	30.85	2.33	−1.314	15.470‡	1.047
Maleckar09	1.07	1.01	0.94	−0.101‡	0.067	N/A
Shannon04*	8.08	8.68	1.07	−0.204	0.016	0.210‡
Iribe06*	0.84	2.66	3.17	0.028	0.130‡	N/A
Matsuoka03*	2.56	2.73	1.07	−0.406	1.615‡	N/A
Noble98	1.67	0.94	0.57	−0.144	0.210‡	N/A
Hinch04†	3.17	6.47	2.04	−1.592	2.451‡	N/A
Pandit01	33.32	57.87	1.74	−0.001	0.062	0.073‡
Pasek08	3.40	6.52	1.92	−1.923	3.037‡	1.239

^*RyR open probability is also modulated by Ca²⁺ in the SR.

^†Model uses rapid equilibrium approximation for the dyadic subspace. The total Ca²⁺ (Ca_Tot) in the cell varied from 0.84 to 33.32 fmol in the presented original models. The threshold for obtaining CaOSS in the reduced models varied from 57% to 317% of the baseline Ca_Tot level. An increase in RyRs (transfer rate or open probability) decreased the level of Ca_Tot necessary for inducing DADs, whereas an increase in sarco(endo)plasmic Ca²⁺-ATPase (SERCA) activity or diffusion from the dyadic subspace to the cytosol was found to increase the threshold.

^‡Most sensitive change for each model. Besides the need of an threefold increase in Ca_Tot for DADs, the Iribe06 model also has high sensitivities for cytosolic buffer capacities and k_NaCa, in contrast to all other models, and it showed an increase of threshold with an increase in k_RyR (this could be due to numerical accuracy). In general, changes in buffer capacities, the transfer rate from the network SR to the junctional SR, and k_NaCa did not change the threshold significantly (not shown), and sensitivities to RyR open probability were similar to the ones of RyR conductances (k_RyR; not shown). N/A, not applicable.