Phosphatidylinositol 4,5-bisphosphate (PIP2) has been suggested to play an important role as an endogenous regulator of ATP-sensitive potassium (K(ATP)) channels consisting of Kir6.2 as a pore-forming subunit. These studies show the ability of PIP2 to activate K(ATP) channel activity and to counteract the inhibitory effect of ATP, implying that PIP2 could serve the function of modulating the sensitivity of K(ATP) channels to the cytoplasmic free ATP concentration. Careful examination of the literature reveals that the definitive physiologically relevant experiments to establish efficacy of PIP2 on this channel may still have to be performed. Our reservations are based on the handling of PIP2 in cell-free experiments and in various strategies designed to modulate PIP2 concentrations in intact cells. Furthermore, a potent stimulatory effect of phosphatidylinositol 3,4,5-trisphosphate, a downstream metabolite of PIP2, on K(ATP) channel activity raises the possibility that the effects on the K(ATP) channel may not be directly related to PIP2.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism