Phosphoinositide sensitivity of ion channels, a functional perspective

Phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] are required for the activity of many different ion channels. This chapter will highlight various aspects of this paradigm, by discussing current knowledge on four different ion channel families: inwardly rectifying K+ (Kir) channels, KCNQ voltage gated K+ channels, voltage gated Ca2+ (VGCC) channels and Transient Receptor Potential (TRP) channels. Our main focus is to discuss functional aspects of this regulation, i.e. how changes in the concentration of PtdIns(4,5)P2 in the plasma membrane upon phospholipase C activation may modulate the activity of ion channels, and what are the major determinants of this regulation. We also discuss how channels act as coincidence detectors sensing phosphoinositide levels and other signalling molecules. We also briefly discuss the available methods to study phosphoinositide regulation of ion channels, and structural aspects of interaction of ion channel proteins with these phospholipids. Finally, in several cases the effect of PtdIns(4,5)P2 is more complex than a simple dependence of ion channel activity on the lipid, and we will discuss some these complexities.