G protein-coupled receptors (GPCR) signaling is precisely timed. This can be achieved at the level of the G protein activation and/or at the receptor level. At the receptor level, classical desensitization is believed to be controlled by a decrease in receptors number in the membrane: Activated receptors are phosphorylated by GPCR-kinase (GRK), tagging them for arrestin binding. This in-turn leads to clathrin-mediated receptor endocytosis. This multisteps process is extended in time (min), and is dependent on initial GPCR phosphorylation by GRK. In contrast, effector regulation is controlled at much faster time scale (s). Here we used the G protein-coupled inwardly rectifying K+ channels (GIRK), as an effector model for GPCR activation, to achieve real-time readout, in intact cells, of GPCR-mediated effector regulation. Upon GIRK activation, currents were desensitized within seconds. This regulation may serve as fast negative feedback for GPCR activation. Here we show that GIRK desensitization rates are dependent on GRK2 activity. GRK2 accelerates desensitization of currents induced by some Gαi/o coupled receptors, but not all. In contrast, silencing endogenous GRK2, results in a decreased in the desensitization rates. A dominant-negative mutant lacking kinase activity did not affect the ability of GRK2 to accelerate currents desensitization, suggesting the lack of GPCR classical desensitization in this process. In contrast, GRK2 mutant displaying limited Gβγ binding affinity, failed to accelerate current desensitization.Measuring simultaneously membrane fluorescence signals from cells expressing GFP-GRK2 and GIRK activity under TIRF microscopy and electrophysiological recordings, respectively, show that GFP-GRK2 membrane recruitment and GIRK desensitization occurs simultaneously.We suggest that GPCR activation induces GRK2 recruitment to the membrane, where it competes with GIRK for Gβγ, to result in short-term current desensitization. The results will be discussed in terms of a novel mechanism of selective regulation of effectors by GPCRs.