The activation of mouse adult-type mouse AChRs is described by a closed cycle (Fig. 1)\cite{29078356}. Without any bound agonists, the free energy change in the resting to activeeric transition (G0) is uphill by +8.3 kcal/mol.  ACh interacts weakly with resting binding sites (GLA =-5.1 kcal/mol) and strongly with active ones  (GHA=-10.2 kcal/mol). Hence, when a  resting receptor having with bound neurotransmitter molecules activates spontaneously, a chemical free energy of (GHA-GLA) generated per binding site.  These AChRs have two nearly-identical neurotransmitter binding sites, so the resting-to-active transition with 2 bound ACh is downhill (G2= -1.9 kcal/mol). Hence, as synapses there is almost no activity (P~10-6)  until ACh is released from the motor nerve terminal, to generate nearly-full activity(P~0.96). Experiments show that no external energy sources  influence  the cycle's balance, the resting and active states are the same with or without bound agonists, and the 2 neurotransmitter binding sites operate independently.
 The binding energy difference, GHA-GLA, determines the extent to which a receptor can be activated above the basal level. For the weak partial agonist choline, an ACh precursor and breakdown product that is present at synapses, GLA=-3.3 and GHA=-6.6, so only -6.6 kcal/mol is addded to the +8.3 starting balance. With 2 =bound choline molecles, the reaction remain uphill (+1.7 kcal/mol) and the activity remains low (P~0.05).