G protein-activated K + channel (GIRK) subunits possess a conserved extracellular integrin-binding motif (RGD) and bind directly to # #1 integrins. We expressed GIRK1/GIRK4 channels labeled with green fluorescent protein in fibroblast cell lines expressing or lacking # #1 integrins. Neither plasma membrane localization nor agonist-evoked GIRK currents were affected by the absence of # #1 integrins or by incubation with externally applied RGD-containing peptide. Mutation of the aspartate (D) of RGD impaired currents, GIRK glycosylation, and membrane localization, but the interaction with # #1 integrins remained intact. Thus, # #1 integrins are not essential for functional GIRK expression ; and the GIRK-integrin interactions involve structural elements other than the RGD motif. z 2000 Federation of European Biochemical Societies. ### ###### Voltage clamp ; Inward rectier K channel ; Fibroblast ; Green uorescent protein 1