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TRPM4  -  transient receptor potential cation...

Homo sapiens

Synonyms: Calcium-activated non-selective cation channel 1, FLJ20041, LTRPC4, LTrpC-4, LTrpC4, ...
 
 
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High impact information on TRPM4

  • TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization [1].
  • Conversely, activation of the phospholipase C (PLC)-coupled M1 muscarinic receptor or pharmacological depletion of cellular PIP2 potently inhibited currents through TRPM4 [2].
  • Here, we describe the identification and characterization of an additional TRPM protein TRPM4 [3].
  • Substitution of this six-amino acid stretch with the selectivity filter of TRPV6 (TIIDGP) resulted in a functional channel that combined the gating hallmarks of TRPM4 (activation by Ca(2+), voltage dependence) with TRPV6-like sensitivity to block by extracellular Ca(2+) and Mg(2+) as well as Ca(2+) permeation [4].
  • Neutralization of Asp(984) resulted in a non-functional channel with a dominant negative phenotype when coexpressed with wild type TRPM4 [4].
 

Biological context of TRPM4

  • We identified five Ca(2+)-calmodulin binding sites in TRPM4 and showed that deletion of any of the three C-terminal sites strongly impaired current activation by reducing Ca(2+) sensitivity and shifting the voltage dependence of activation to very positive potentials [5].
  • Thus, the Ca(2+) sensitivity of TRPM4 is regulated by ATP, PKC-dependent phosphorylation, and calmodulin binding at the C terminus [5].
  • Voltage dependence of TRPM4 may be functionally important, especially in excitable tissues generating plateau-like or bursting action potentials [6].
  • TRPM4 regulates calcium oscillations after T cell activation [7].
  • TRPM4 is a Ca(2+)-activated nonselective cation channel that regulates membrane potential in response to intracellular Ca(2+) signaling [8].
 

Anatomical context of TRPM4

  • Regulation of Ca2+ entry is a key process for lymphocyte activation, and TRP channels may both increase Ca2+ influx (such as TRPC3) or decrease Ca2+ influx through membrane depolarization (such as TRPM4) [9].
  • TRPM4 controls insulin secretion in pancreatic beta-cells [10].
 

Associations of TRPM4 with chemical compounds

  • We reveal that TRPM4 and MLSN each mediate Ca(2+) entry when expressed in HEK293 cells [3].
  • PIP2 shifted the voltage dependence of TRPM4 activation towards negative potentials and increased the channel's Ca2+ sensitivity 100-fold [2].
  • Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization [8].
  • Poly-l-lysine, a PI(4,5)P(2) scavenger, caused rapid desensitization, whereas MgATP, at concentrations that activate lipid kinases, promoted recovery of TRPM4 currents [8].
  • We have tested the effects of decavanadate (DV), a compound known to interfere with ATP binding in ATP-dependent transport proteins, on TRPM4, a Ca(2+)-activated, voltage-dependent monovalent cation channel, whose activity is potently blocked by intracellular ATP(4-) [11].
 

Regulatory relationships of TRPM4

 

Other interactions of TRPM4

  • All TRP channels, except for TRPM4 and TRPM5, are cation channels that allow Ca2+ influx [13].
  • This review discusses some features of voltage-dependent gating of TRPV1, TRPM4 and TRPM8 [14].
 

Analytical, diagnostic and therapeutic context of TRPM4

  • From cardiac cation channels to the molecular dissection of the transient receptor potential channel TRPM4 [15].

References

  1. TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Launay, P., Fleig, A., Perraud, A.L., Scharenberg, A.M., Penner, R., Kinet, J.P. Cell (2002) [Pubmed]
  2. The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate. Nilius, B., Mahieu, F., Prenen, J., Janssens, A., Owsianik, G., Vennekens, R., Voets, T. EMBO J. (2006) [Pubmed]
  3. Regulation of melastatin, a TRP-related protein, through interaction with a cytoplasmic isoform. Xu, X.Z., Moebius, F., Gill, D.L., Montell, C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. The selectivity filter of the cation channel TRPM4. Nilius, B., Prenen, J., Janssens, A., Owsianik, G., Wang, C., Zhu, M.X., Voets, T. J. Biol. Chem. (2005) [Pubmed]
  5. Regulation of the Ca2+ sensitivity of the nonselective cation channel TRPM4. Nilius, B., Prenen, J., Tang, J., Wang, C., Owsianik, G., Janssens, A., Voets, T., Zhu, M.X. J. Biol. Chem. (2005) [Pubmed]
  6. Voltage dependence of the Ca2+-activated cation channel TRPM4. Nilius, B., Prenen, J., Droogmans, G., Voets, T., Vennekens, R., Freichel, M., Wissenbach, U., Flockerzi, V. J. Biol. Chem. (2003) [Pubmed]
  7. TRPM4 regulates calcium oscillations after T cell activation. Launay, P., Cheng, H., Srivatsan, S., Penner, R., Fleig, A., Kinet, J.P. Science (2004) [Pubmed]
  8. Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization. Zhang, Z., Okawa, H., Wang, Y., Liman, E.R. J. Biol. Chem. (2005) [Pubmed]
  9. TRP channels in lymphocytes. Schwarz, E.C., Wolfs, M.J., Tonner, S., Wenning, A.S., Quintana, A., Griesemer, D., Hoth, M. Handbook of experimental pharmacology (2007) [Pubmed]
  10. TRPM4 controls insulin secretion in pancreatic beta-cells. Cheng, H., Beck, A., Launay, P., Gross, S.A., Stokes, A.J., Kinet, J.P., Fleig, A., Penner, R. Cell Calcium (2007) [Pubmed]
  11. Decavanadate modulates gating of TRPM4 cation channels. Nilius, B., Prenen, J., Janssens, A., Voets, T., Droogmans, G. J. Physiol. (Lond.) (2004) [Pubmed]
  12. TRPM5 and taste transduction. Liman, E.R. Handbook of experimental pharmacology (2007) [Pubmed]
  13. Recent developments in vascular endothelial cell transient receptor potential channels. Yao, X., Garland, C.J. Circ. Res. (2005) [Pubmed]
  14. Gating of TRP channels: a voltage connection? Nilius, B., Talavera, K., Owsianik, G., Prenen, J., Droogmans, G., Voets, T. J. Physiol. (Lond.) (2005) [Pubmed]
  15. From cardiac cation channels to the molecular dissection of the transient receptor potential channel TRPM4. Nilius, B., Vennekens, R. Pflugers Arch. (2006) [Pubmed]
 
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