Phosphatidylinositol 4,5-bisphosphate and ATP-sensitive potassium channel regulation - A word of caution

sPhosphatidylinositol 4,5-bisphosphate (PIP2) has been suggested to play an important role as an endogenous regulator of ATP-sensitive potassium (K-AT P) channels consisting of Kir6.2 as a pore-forming subunit, These studies s how the ability of PIP2 to activate K-ATP channel activity and to counterac t the inhibitory effect of ATP, implying that PIP2 could serve the function of modulating the sensitivity of KATP channels to the cytoplasmic free ATP concentration, Careful examination of the literature reveals that the defi nitive physiolo&ically relevant experiments to establish efficacy of PIP2 o n this channel may still have to be performed. Our reservations are based o n the handling of PIP2 in cell-free experiments and ill various strategies designed to modulate PIP2 concentrations in intact cells. Furthermore, a po tent stimulatory effect of phosphatidylinositol 3,4,5-trisphosphate, a down stream metabolite of PIP2, on K-ATP channel activity raises the possibility that the effects on the K-ATP channel mag not be directly related to PIP2.