Regulation of KCNQ channels by manipulation of phosphoinositides

J Physiol. 2007 Aug 1;582(Pt 3):911-6. doi: 10.1113/jphysiol.2007.132647. Epub 2007 Apr 5.


Activation of phospholipase C (PLC) through G-protein-coupled receptors produces a large number of second messengers and regulates many physiological processes. Many membrane proteins including ion channels require the phosphoinositide phosphatidylinositol 4,5-bisphosphate (PIP(2)) to function. Activation of PLC can shut down their activity if it depletes the PIP(2) pool strongly. Such a mechanism accounts for the muscarinic suppression of current in KCNQ channels. We describe a variety of methods used to show that these channels require PIP(2) and that current in the channels is suppressed when receptor-activated PLC depletes PIP(2). The methods include observing translocation of lipid-sensitive protein domains, overexpression of enzymes of phosphoinositide metabolism, engineering these enzymes to move to the plasma membrane in response to a chemical signal, and direct chemical analysis of phospholipids. These approaches are general and can be used to test for PIP(2) requirements of other membrane proteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase / metabolism
  • Animals
  • Homeostasis
  • Humans
  • KCNQ Potassium Channels / physiology*
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phosphatidylinositols / physiology*
  • Second Messenger Systems / physiology
  • Type C Phospholipases / metabolism


  • KCNQ Potassium Channels
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols
  • 1-Phosphatidylinositol 4-Kinase
  • Type C Phospholipases