Subsequent studies have taken advantage of GIRK channel knockout mice (see Table 1). In GIRK2−/− mice, for example, the dose-response curve for morphine and clonidine (an α2AR agonist) analgesia is shifted to higher concentrations, while the maximal effect was preserved137. This finding was confirmed in a recent study using a GIRK2/3 double knockout mouse30; in these mice the potency (coupling efficiency) of opioid-analgesia was reduced, but their efficacy (maximal response) was intact.
