The Heterogeneous Kinetic Origins of the Binding Properties of Orthosteric Ligands at Heteromeric Nicotinic Acetylcholine Receptors.

A plethora of agonists and competitive antagonists have been developed to explore the therapeutic potential in neuronal nicotinic acetylcholine receptors (nAChRs). Based on equilibrium and kinetic [H]epibatidine binding studies, we report that the kinetic fingerprints of [H]epibatidine at five heteromeric αβ nAChRs and of seven classical agonists at α4β2 and α3β4 nAChRs differ substantially. While this diversity depends on both the agonist and receptor subtype, the overall pattern of kinetic determinants emerging from this profiling is complex.