5wp6

Structural highlights

Disease

[TRPM4_HUMAN] Familial progressive cardiac conduction defect;Brugada syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[TRPM4_HUMAN] Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it. Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway.^{[1] [2] [3] [4] [5] [6] [7] [8]}

References

1. ↑ Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP. TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell. 2002 May 3;109(3):397-407. PMID:12015988
2. ↑ Nilius B, Prenen J, Droogmans G, Voets T, Vennekens R, Freichel M, Wissenbach U, Flockerzi V. Voltage dependence of the Ca2+-activated cation channel TRPM4. J Biol Chem. 2003 Aug 15;278(33):30813-20. Epub 2003 Jun 10. PMID:12799367 doi:http://dx.doi.org/10.1074/jbc.M305127200
3. ↑ Guinamard R, Chatelier A, Demion M, Potreau D, Patri S, Rahmati M, Bois P. Functional characterization of a Ca(2+)-activated non-selective cation channel in human atrial cardiomyocytes. J Physiol. 2004 Jul 1;558(Pt 1):75-83. Epub 2004 Apr 30. PMID:15121803 doi:http://dx.doi.org/10.1113/jphysiol.2004.063974
4. ↑ Earley S, Waldron BJ, Brayden JE. Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries. Circ Res. 2004 Oct 29;95(9):922-9. Epub 2004 Oct 7. PMID:15472118 doi:http://dx.doi.org/01.RES.0000147311.54833.03
5. ↑ Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet JP. TRPM4 regulates calcium oscillations after T cell activation. Science. 2004 Nov 19;306(5700):1374-7. doi: 10.1126/science.1098845. PMID:15550671 doi:http://dx.doi.org/10.1126/science.1098845
6. ↑ Cheng H, Beck A, Launay P, Gross SA, Stokes AJ, Kinet JP, Fleig A, Penner R. TRPM4 controls insulin secretion in pancreatic beta-cells. Cell Calcium. 2007 Jan;41(1):51-61. Epub 2006 Jun 27. PMID:16806463 doi:http://dx.doi.org/S0143-4160(06)00105-9
7. ↑ Armisen R, Marcelain K, Simon F, Tapia JC, Toro J, Quest AF, Stutzin A. TRPM4 enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. J Cell Physiol. 2011 Jan;226(1):103-9. doi: 10.1002/jcp.22310. PMID:20625999 doi:http://dx.doi.org/10.1002/jcp.22310
8. ↑ Weber KS, Hildner K, Murphy KM, Allen PM. Trpm4 differentially regulates Th1 and Th2 function by altering calcium signaling and NFAT localization. J Immunol. 2010 Sep 1;185(5):2836-46. doi: 10.4049/jimmunol.1000880. Epub 2010, Jul 23. PMID:20656926 doi:http://dx.doi.org/10.4049/jimmunol.1000880