Phosphoinositides regulate ion channels

Biochim Biophys Acta. 2015 Jun;1851(6):844-56. doi: 10.1016/j.bbalip.2014.09.010. Epub 2014 Sep 18.


Phosphoinositides serve as signature motifs for different cellular membranes and often are required for the function of membrane proteins. Here, we summarize clear evidence supporting the concept that many ion channels are regulated by membrane phosphoinositides. We describe tools used to test their dependence on phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate, and consider mechanisms and biological meanings of phosphoinositide regulation of ion channels. This lipid regulation can underlie changes of channel activity and electrical excitability in response to receptors. Since different intracellular membranes have different lipid compositions, the activity of ion channels still in transit towards their final destination membrane may be suppressed until they reach an optimal lipid environment. This article is part of a Special Issue entitled Phosphoinositides.

Keywords: Calcium channel; G-protein coupled receptor (GPCR); Phosphatidylinositol 4,5-bisphosphate; Phospholipase C (PLC); Potassium channel; Transient receptor potential channel (TRP channel).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Epithelial Sodium Channels / genetics
  • Epithelial Sodium Channels / metabolism*
  • Gene Expression Regulation
  • Humans
  • Ion Transport
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / metabolism*
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism


  • Calcium Channels
  • Chloride Channels
  • Epithelial Sodium Channels
  • Phosphatidylinositol 4,5-Diphosphate
  • Potassium Channels
  • Receptors, G-Protein-Coupled
  • Transient Receptor Potential Channels
  • Type C Phospholipases