Figure 1.

Receptor-induced activation of GIRK currents. (A) m4R and μ-opioid receptor (μOR) activated GIRK current in the same cell with different kinetics of activation and desensitization. The concentrations (in μM) of agonists used are shown in parentheses. (B) Acute desensitization also was observed via perforated patch recording of HEK 293 cells (m4R, Upper) or two-electrode voltage clamp in Xenopus oocytes (α_2A adrenergic receptor, Lower). (C) Activation of GIRK current by GTP in the excised inside-out patches from oocytes is sensitive to pertussis toxin (PTX). (D) Larger activated currents and acute desensitization were observed in the patches excised from cells expressing higher levels of receptors. (E) In a patch membrane with a high level of μOR even the partial agonist nalorphine (50 nM) could evoke acute desensitization of GIRK current when the solution was changed from nucleotide free to one containing GTP. (F) In a patch expressing μOR, GIRK1, GIRK2, and RGS4, similar perfusion protocol revealed acute desensitization.