quenching, indicating closure of GIRK2 channels (‘GIRK2/PIP2 + HE’, Fig. 1b). Similarly, pre-incubating GIRK2-containing liposomes with the K channel inhibitor BaCl2 (2 mM) prevented the CCCP-dependent quenching (data not shown). In the absence of PIP2, however, there was no significant change in fluorescence, i.e., no quenching, upon CCCP addition (‘GIRK2’, Fig. 1b). Thus, under these defined conditions of PE/PG lipids and cytoplasmic Na+, brain PIP2 is necessary and sufficient for robust activation of GIRK2 channels12, 14, 35, 36.