Although a high-resolution three-dimensional structure of a full-length GIRK channel is currently not available, structures of the cytoplasmic domains of GIRK1, GIRK2 and a G protein-insensitive inward rectifier (IRK1) have been solved64-66. Comparison of these structures highlights a conserved secondary structure for inwardly rectifying potassium channels, consisting of 14 beta strands and two alpha helices (Figure 2A,B). These cytoplasmic high resolution structures have revealed a new structure, the G loop formed by the βH-βI sheet65, that is important in channel gating65,67,68, and identified several amino acids involved in regulating inward rectification and K+ binding64,69-71. A recent 3D structure of a full-length chimeric channel, containing the transmembrane domains and pore of a bacterial inward rectifier (KirBac1.3) channel, and the cytoplasmic N- and C-terminal domains of GIRK1 has been solved in two different conformations72 revealing the relative position of the pore (selectivity filter), G-loop and M2 gates, and the cytoplasmic interaction sites (Figure 2A). Notably, these crystals revealed two different positions of the G loop, which have been tentatively ascribed to putative open and closed states of the channel72. Though more studies
