Human AChRs REFERs. The slope (φ) of each REFER reports the extent to which a change in equilibrium constant is caused by a change in the forward versus backward rate constant. (a) Binding to the resting state. k_on (M⁻¹s⁻¹), association rate constant; K_dR, equilibrium dissociation constant. At all sites, agonists differ mainly with regard to association rate constant (ACh-class more so than Epi-class agonists). (b) Gating with one bound agonist. f₁ (s⁻¹), forward, channel-opening rate constant; E₁, monoliganded gating equilibrium constant. At all sites, agonists differ mainly with regard to the channel-opening rate constant (Epi-class more so than ACh-class agonists).