Activation of inwardly rectifying potassium (Kir) channels by phosphatidylinosital-4,5-bisphosphate (PIP2): Interaction with other regulatory ligands

All members of the inwardly rectifying potassium channels (Kir1-7) are regulated by the membrane phospholipid, phosphatidylinosital-4,5-bisphosphate (PIP2). Some are also modulated by other regulatory factors or ligands such as ATP and G-proteins, which give them their common names, such as the ATP sensitive potassium (KATP) channel and the G-protein gated potassium channel. Other more non-specific regulators include polyamines, kinases, pH and Na+ ions. Recent studies have demonstrated that PIP2 acts cooperatively with other regulatory factors to modulate Kir channels. Here we review how PIP2 and co-factors modulate channel activities in each subfamily of the Kir channels.