TRPM4


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TRPM4

A gene on chromosome 19q13.33 that encodes a calcium-activated nonselective (CAN) cation channel, which mediates membrane depolarisation of cardiac myocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells and others. TRPM4 participates in T-cell activation by modulating Ca2+ after T-cell activation, which is required for NFAT-dependent IL2 production; it controls insulin secretion, and it may be involved in cardiac pacing or trigger arrhythmias in the face of Ca2+ overload. It also affects T-helper (Th1 and Th2) cell motility and cytokine production by differential regulation of calcium signalling and NFATC1 localisation. It enhances cell proliferation by upregulating the beta-catenin-signalling pathway.
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References in periodicals archive ?
Rougier, "TRPM4 channels in the cardiovascular system: physiology, pathophysiology, and pharmacology," Biochemical Pharmacology, vol.
Critical role for transient receptor potential channel TRPM4 in myogenic constriction of cerebral arteries.
Marabita and Islam demonstrated that human [beta]-cells express at least eight TRP channels, for example, TRPC1, TRPM4, TRPM7, TRPM2, TRPM3, TRPP2, TRPML1, and TRPML3 [3].
Although 9-phenanthrol was initially discovered as an inhibitor of the TRPM4 channels, later studies showed that it also inhibits the transmembrane protein 16A (TMEM16A), a [Ca.sup.2+]-activated [Cl.sup.-] channel [7].
The fact that 20-30 [micro]M 9phenanthrol inhibited insulin secretion is consistent with the fact that the inhibition of insulin secretion was due to the inhibition of the TRPM4 channels because the IC50 of 9-phenanthrol for the transfected or the endogenous TRPM4 channels has been shown to be 20-30 [micro]M in many cells [5, 6].
As mentioned earlier, this channel is also inhibited by 9-phenanthrol at similar concentrations that inhibit the TRPM4 channel [7].
We have demonstrated that 9-phenanthrol, an inhibitor of the TRPM4 and the TMEM16A channels and an activator of the [K.sub.ca]3.1 channel, strongly inhibits both the glucose-and the GLP-1-induced insulin secretion.
Del Negro, "The TRPM4 channel inhibitor 9-phenanthrol," British Journal of Pharmacology, vol.
Norez et al., "9-phenanthrol inhibits human TRPM4 but not TRPM5 cationic channels," British Journal of Pharmacology, vol.
Genetic sequencing showed that no known mutation of cardiomyopathy was detected, but he had three mutant heterozygotes in TGFBR2 , SMAD9 , TRPM4 gene which did not find a link with this disease.
Shigeto et al.: GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation.
Protein kinase C regulates vascular myogenic tone through activation of TRPM4. Am J Physiol Heart Circ Physiol 2007; 292: H2613-H2622, doi: 10.1152/ajpheart.01286.2006.