Figure 3.

MOR desensitization is mediated independently by ERK1/2 and βarr-2. A–D, Recordings of LC neurons from βarr-2 k.o. (A, C) and w.t. (B, D) mice show desensitization during exposure to ME (30 μm, 10 min). GRK2i alone had no effect on MOR desensitization in βarr-2 k.o. (Aii, C) or w.t. (Bii, D). ERK1/2 inhibitors (ERK1/2i) alone nearly abolished MOR desensitization in βarr-2 k.o. (Aiii, C) but only weakly reduced MOR desensitization in w.t. (Biii, D). Aiv, Biv, Blocking GRK2 and ERK1/2 together nearly abolished MOR desensitization in both groups (C, D). Calibrations: 5 min, 25 pA. Arrows denote desensitized currents. C, D, Mean ± SEM, n shown inside bars, t tests; n.s, nonsignificant; p > 0.05, *p < 0.05, ***p < 0.0001.