Fig. 1.

Coupling of the CB1 receptor to the G-protein-activated inward rectifier potassium channels K_ir3.1 and K_ir3.4. A, Representative trace showing the change in current during a typical experiment. A large inward current was apparent as the K⁺ concentration was increased from 2 to 16 mm in normal oocyte saline buffer. WIN (1 μm) in the buffer (16 mm K⁺) further increased the current. To detect any change in basal current after the agonist treatment (8 min), SR 141716A (1 μm), a CB1 receptor antagonist, was applied to displace WIN and reverse CB1-mediated activation of the current. The interpolated decrease in baseline current was plotted, as shown by the dashed line. The amount of desensitization was calculated as the percent change in response to WIN after 8 min. Current traces presented in subsequent figures show only the agonist-activated current adjusted for the change in baseline. B, WIN activation of inwardly rectifying K⁺ channels. TheI–V relationship was generated by steps from −140 to 40 mV after subtracting the current at the same potential in 16 mm K⁺ buffer. C, Concentration–response curve of WIN. Cumulatively higher concentrations of WIN were applied to the bath followed by perfusion with SR 141716A (1 μm). The agonist response at each concentration was normalized as a percentage of the maximal WIN response. Each point represents the mean response measured in 10–14 different oocytes.