Table 1. Mathematical Model Parameters.

Buffering & Scaling
Symbol	Value	Description	Reference
fc	0.01	Cytosolic Ca2+ buffering	[38]
fER	0.025	ER Ca2+ buffering	[38]
γ	9	cytosol/ ER volume ratio	[39]
Plasma Membrane Fluxes
JINleak	0.15 μMs-1	Inward leak across plasma membrane	Fitted†
vPMCA	30 μMs-1	Maximum PMCA activation	Fitted†
kPMCA	0.45 μM	PMCA Ca2+ affinity	[32]
ER Fluxes
vSERCA	22.5 μMs-1	Maximum SERCA activation	Fitted†
kSERCA	0.105 μM	SERCA Ca2+ affinity	[32]
vERleak	0.03 s-1	Rate of Ca2+ leak across ER membrane	Fitted†
Li Rinzel IP3R Models
d1	0.13 μM	IP3 dissociation constant (Ca2+ unbound from inactivation site)	[24]
d2	1.049 μM	Ca2+ dissociation constant from the inactivation site (IP3 bound)	[24]
d3	0.9434 μM	IP3 dissociation constant (Ca2+ bound to inactivation site)	[24]
d5	0.08234 μM	Ca2+ dissociation constant from activation site	[24]
a2	0.2 μMs-1	Ca2+ binding rate to the inactivation site	[24]
vIP3R	15 μMs-1	Maximum flux through IP3Rs	Fitted†
P2X7R Model
gX7	2.5x10-8 Ms-1	P2X7R conductance of both naïve and sensitized open states	Adjusted***
E	0 mV	Reversal potential	[18]
k1	0.3 s-1	Transition rates between states (Fig 3B, along the same row)	[18]
k2	1265 M-1s-1		[18]*
k3	2.4 s-1		[18]
k4	1581 M-1s-1		[18]*
k5	1.58 s-1		[18]
k6	221 M-1s-1		[18]*
k7	316 M-1s-1		[18]*
L1	0.0001	Transition rates between naïve (Fig 3B, middle row) and sensitized (Fig 3B, bottom row)	[18]
L2	0.004		[18]
L3	0.3		[18]
H1	0.001	Transition rates between naïve (Fig 3B, middle row) and desensitized (Fig 3B, upper row)	[18]
H2(C2)	0.01		[18]
H2(Q1)	0.05		Adjusted***
H2(Q2)	0.8		Adjusted***
V	-0.06 V	Membrane Potential	[18]
fCa	0.046	Fraction of P2X7R flux that is Ca2+	[36]
Vosteo	6.5 pL	Osteoblast volume	[35,40]
IP3 Dynamics
αATP	0.03 μMs-1	Maximum rate of IP3 production driven by ATP	[30,41]**
kATP	1 μM	Sensitivity of IP3 production to [ATP]	Fitted†
δ	0.01 s-1	Degradation rate of IP3	[30,41]**

*Parameter values in [18] were fitted to BzATP. To capture the lower binding affinity of ATP to P2X7R, these parameter values were rescaled here (by dividing them by the factor 31.625).

**Parameter values from [30] were used as an upper bound for the parameters in this work, based on the significantly slower IP₃ dynamics reported in living cells in [41].

*** As stated in the text, these values were adjusted due to the evidence that P2X7R do not dilate and that P2X7R desensitization increases with more ATP binding.

†These parameter values were determined by fitting the model to data of dose-responses of ATP-induced [Ca²⁺]_i elevations shown in Fig 7.