Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase

► The AMP-activated protein kinase (AMPK) down-regulates the inward rectifier K+ channel Kir2.1. ► Kir2.1 is similarly down-regulated by constitutively active γR70QAMPK but not by inactive mutant αK45RAMPK. ► AMPK decreases the Kir2.1 protein abundance in the cell membrane. ► Kir2.1 is down-regulated by the ubiquitin ligase Nedd4-2. ► AMPK augments the effect of wild type Nedd4-2 but not of Nedd4-2S795A lacking the AMPK phosphorylation site.