. 2019 Jan;95(1):70–81. doi: 10.1124/mol.118.113464

TABLE 2.

Effects of agonist combinations on open probability

The columns give the paired agonists (agonists 1 and 2) and adjusted concentrations, open probabilities for each agonist separately (P_{open,agonist 1} and P_{open,agonist 2}) or combined (P_{open,agonist 1+agonist 2}), and the predicted P_open value assuming the paired agonists act through the same or distinct sites. The column labeled LR shows the likelihood ratio (LR = e^LLR) that quantifies by how many times the model with distinct sites is more likely than the model with the same sites to describe the data (and in parentheses the inverse of that likelihood ratio). The value of parameter Δ (see Materials and Methods) indicates the empirical support for the lower ranked model. Values of Δ of 4–7 are considered to indicate little empirical support and values of >10 indicate essentially no support (Burnham and Anderson, 2004). The data show mean ± S.D. from five to nine cells at each condition. The nominal concentrations of agonists are provided in the text. The predicted P_open values were not calculated for GABA + propofol and alfaxalone + propofol (N/A) using a model assuming the same sites because the number of binding sites is different for the agents in both pairs.

Adjusted Concentration		P_{open,agonist 1}	P_{open,agonist 2}	P_{open,agonist 1+agonist 2}	Predicted P_open		LR	Δ
Agonist 1	Agonist 2	P_{open,agonist 1}	P_{open,agonist 2}	P_{open,agonist 1+agonist 2}	Same Site	Distinct Site	LR	Δ
μM	μM
GABA (2.2)	propofol (9.4)	0.013 ± 0.007	0.011 ± 0.004	0.47 ± 0.19	N/A	0.48 ± 0.24	N/A	N/A
GABA (2.8)	pentobarbital (67)	0.021 ± 0.016	0.013 ± 0.013	0.63 ± 0.11	0.052 ± 0.043	0.53 ± 0.25	1209 (8.3 × 10⁻⁴)	14
GABA (6.8)	alfaxalone (0.97)	0.083 ± 0.022	0.0008 ± 0.0005	0.36 ± 0.05	0.054 ± 0.011	0.35 ± 0.21	39 (0.026)	7
GABA (4.0)	P4S (45)	0.034 ± 0.004	0.049 ± 0.009	0.059 ± 0.010	0.085 ± 0.009	0.93 ± 0.02	<10⁻⁶ (>10⁶)	35
GABA (3.0)	β-alanine (206)	0.021 ± 0.002	0.024 ± 0.004	0.054 ± 0.011	0.074 ± 0.010	0.80 ± 0.04	<10⁻⁶ (>10⁶)	36
alfaxalone (0.29)^a	3α5αP (0.07)^a	0.032 ± 0.16	0.034 ± 0.014	0.053 ± 0.022	0.053 ± 0.024	0.09 ± 0.04	2.5 × 10⁻⁵ (39,883)	21
3α5αP (0.17)^a	3α5βP (0.26)^a	0.052 ± 0.011	0.044 ± 0.010	0.074 ± 0.013	0.071 ± 0.014	0.18 ± 0.06	<10⁻⁶ (>10⁶)	37
3α5βP (0.28)^a	ent-3α5βP (0.80)^a	0.10 ± 0.02	0.12 ± 0.03	0.17 ± 0.03	0.16 ± 0.03	0.36 ± 0.08	<10⁻⁶ (>10⁶)	30
alfaxalone (0.15)^b	etiocholanolone (7.5)^b	0.18 ± 0.02	0.15 ± 0.01	0.19 ± 0.01	0.19 ± 0.01	0.23 ± 0.03	4.7 × 10⁻⁴ (2134)	15
alfaxalone (0.20)^a	propofol (1.2)^a	0.18 ± 0.09	0.23 ± 0.12	0.31 ± 0.12	N/A	0.37 ± 0.17	N/A	N/A
alfaxalone (0.63)	propofol (31)	0.0006 ± 0.0001	0.10 ± 0.03	0.38 ± 0.03	N/A	0.33 ± 0.10	N/A	N/A
alfaxalone (0.14)^a	pentobarbital (5.3)^a	0.12 ± 0.04	0.19 ± 0.07	0.30 ± 0.13	0.23 ± 0.07	0.28 ± 0.08	16.4 (0.061)	6
alfaxalone (0.63)	pentobarbital (172)	0.0006 ± 0.0001	0.057 ± 0.025	0.35 ± 0.09	0.042 ± 0.018	0.21 ± 0.10	228 (0.0044)	11

LR, likelihood ratio.

^{^a}

The experiments with alfaxalone + 3α5αP, 3α5αP + 3α5βP, and 3α5βP + ent-3α5βP, and sets of experiments with alfaxalone + propofol, and alfaxalone + pentobarbital were conducted in the presence of a low concentration of GABA.

^{^b}

The experiments with alfaxalone + etiocholanolone were conducted on receptors containing the gain-of-function α1(L263S) mutation in both α subunits.