The TRPM7 channel is inactivated by PIP(2) hydrolysis

Nat Cell Biol. 2002 May;4(5):329-36. doi: 10.1038/ncb781.


TRPM7 (ChaK1, TRP-PLIK, LTRPC7) is a ubiquitous, calcium-permeant ion channel that is unique in being both an ion channel and a serine/threonine kinase. The kinase domain of TRPM7 directly associates with the C2 domain of phospholipase C (PLC). Here, we show that in native cardiac cells and heterologous expression systems, G alpha q-linked receptors or tyrosine kinase receptors that activate PLC potently inhibit channel activity. Numerous experimental approaches demonstrated that phosphatidylinositol 4,5-bisphosphate (PIP(2)), the substrate of PLC, is a key regulator of TRPM7. We conclude that receptor-mediated activation of PLC results in the hydrolysis of localized PIP(2), leading to inactivation of the TRPM7 channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbachol / pharmacology
  • Cell Line
  • Cholinergic Agonists / pharmacology
  • Diglycerides / pharmacology
  • Heart / drug effects
  • Humans
  • Hydrolysis
  • Ion Channels / metabolism*
  • Membrane Proteins*
  • Models, Biological
  • Myocardium / cytology
  • Patch-Clamp Techniques
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Protein Kinase C / metabolism
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases
  • Protein Structure, Tertiary
  • Rats
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic / metabolism
  • Recombinant Fusion Proteins / metabolism
  • TRPM Cation Channels
  • Two-Hybrid System Techniques
  • Type C Phospholipases / metabolism*
  • Yeasts / metabolism


  • Cholinergic Agonists
  • Diglycerides
  • Ion Channels
  • Membrane Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic
  • Recombinant Fusion Proteins
  • TRPM Cation Channels
  • Carbachol
  • Protein Kinases
  • Protein Serine-Threonine Kinases
  • TRPM7 protein, human
  • Trpm7 protein, rat
  • Protein Kinase C
  • Type C Phospholipases