TABLE 3

Operational model parameters for the functional allosteric interaction between ACh and BQCA at the M1 mAChR

Estimated parameter values represent the mean ± S.E. of three experiments performed in duplicate and analyzed according to Eq. 2. For this analysis, the pKB value for BQCA was fixed to that determined from the radioligand binding assays.

M1 WTM1 DREADD
Ca2+pERK1/2cAMPCa2+pERK1/2cAMP
Log τAa4.78 ± 0.104.71 ± 0.071.36 ± 0.161.31 ± 0.111.53 ± 0.05ND
Log τBb (τB)3.19 ± 0.05 (1550)2.75 ± 0.03 (560)−0.51 ± 0.30 (0.31)0.30 ± 0.08 (2)0.28 ± 0.06 (2)ND
Log αβc (αβ)4.10 ± 0.20 (12590)3.84 ± 0.17 (6918)2.30 ± 0.14 (200)2.92 ± 0.14 (831)2.40 ± 0.07 (251)ND

  • ND, not determined.

  • ↵a Logarithm of the operational efficacy parameter of the orthosteric agonist.

  • ↵b Logarithm of the operational efficacy parameter of the allosteric agonist.

  • ↵c Logarithm of the cooperativity between ACh and BQCA. Antilogarithm shown in parentheses.