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Regulation of KCNQ channels by manipulation of phosphoinositides
Author(s) -
Suh ByungChang,
Hille Bertil
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.132647
Subject(s) - second messenger system , phosphatidylinositol , chemistry , phospholipase c , microbiology and biotechnology , muscarinic acetylcholine receptor , ion channel , g protein , signal transduction , receptor , biochemistry , biophysics , biology
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.