Mammals express four GIRK channel subunits (GIRK1-4 or Kir3.1-3.4). In the brain, GIRK1-GIRK3 subunits are common (Figure 1B), while GIRK4 expression is low and therefore does not significantly contribute to cerebral GIRK currents10. The three splice variants of GIRK2 that are expressed in the brain, differ in the length of the C-terminal domain: GIRK2c contains a PDZ-binding motif that is absent in GIRK2a and GIRK2b11-14. For clarification, GIRK2a (Kir3.2a) has been previously referred to as GIRK214 and GIRK2-115, while GIRK2c has been previously referred to as KATP-216, GIRK2A-114,15 and BIR117. GIRK1 splice variants exist in the brain but have not been investigated in detail18 and no splice variants have been reported for GIRK3 and GIRK4. GIRK subunits assemble into tetrameric channels in both heterologous expression systems (e.g. Xenopus oocytes, HEK-293 cells) and native tissues3,19-23. Because GIRK1 and GIRK3 subunits are unable to form functional channels on the plasma membrane, they form heterotetrameric channels (GIRK1/3; GIRK2/3)20,24,25 (Figure 1B). GIRK2, on the other hand, is unique because it can form homotetramers11,22,23 and can assembles with other GIRK subunits to form heterotetramers, such as GIRK1/2 and GIRK2/3.
