scholarly journals Transient receptor potential melastatin 3 is a phosphoinositide-dependent ion channel

2015 ◽  
Vol 146 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Doreen Badheka ◽  
Istvan Borbiro ◽  
Tibor Rohacs
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Kinase Inhibitors ◽  
Trp Channels ◽  
Receptor Potential ◽  
Channel Activity ◽  
Intact Cells ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Phosphatidylinositol 4

Phosphoinositides are emerging as general regulators of the functionally diverse transient receptor potential (TRP) ion channel family. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been reported to positively regulate many TRP channels, but in several cases phosphoinositide regulation is controversial. TRP melastatin 3 (TRPM3) is a heat-activated ion channel that is also stimulated by chemical agonists, such as pregnenolone sulfate. Here, we used a wide array of approaches to determine the effects of phosphoinositides on TRPM3. We found that channel activity in excised inside-out patches decreased over time (rundown), an attribute of PI(4,5)P2-dependent ion channels. Channel activity could be restored by application of either synthetic dioctanoyl (diC8) or natural arachidonyl stearyl (AASt) PI(4,5)P2. The PI(4,5)P2 precursor phosphatidylinositol 4-phosphate (PI(4)P) was less effective at restoring channel activity. TRPM3 currents were also restored by MgATP, an effect which was inhibited by two different phosphatidylinositol 4-kinase inhibitors, or by pretreatment with a phosphatidylinositol-specific phospholipase C (PI-PLC) enzyme, indicating that MgATP acted by generating phosphoinositides. In intact cells, reduction of PI(4,5)P2 levels by chemically inducible phosphoinositide phosphatases or a voltage-sensitive 5′-phosphatase inhibited channel activity. Activation of PLC via muscarinic receptors also inhibited TRPM3 channel activity. Overall, our data indicate that TRPM3 is a phosphoinositide-dependent ion channel and that decreasing PI(4,5)P2 abundance limits its activity. As all other members of the TRPM family have also been shown to require PI(4,5)P2 for activity, our data establish PI(4,5)P2 as a general positive cofactor of this ion channel subfamily.

A cell-based impedance assay for monitoring transient receptor potential (TRP) ion channel activity

2011 ◽  
Vol 26 (5) ◽  
pp. 2376-2382 ◽  
Author(s):  
Oliver Pänke ◽  
Winnie Weigel ◽  
Sabine Schmidt ◽  
Anja Steude ◽  
Andrea A. Robitzki
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Channel Activity ◽  
A Cell ◽  
Transient Receptor ◽  
Trp Ion Channel

scholarly journals Volatile anaesthetics inhibit the thermosensitive nociceptor ion channel transient receptor potential melastatin 3 (TRPM3)

2020 ◽  
Vol 174 ◽  
pp. 113826 ◽  
Author(s):  
Balázs Kelemen ◽  
Erika Lisztes ◽  
Anita Vladár ◽  
Martin Hanyicska ◽  
János Almássy ◽  
...  
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Volatile Anaesthetics ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

scholarly journals Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity

2008 ◽  
Vol 28 (8) ◽  
pp. 2637-2647 ◽  
Author(s):  
Jonathan A. Stiber ◽  
Zhu-Shan Zhang ◽  
Jarrett Burch ◽  
Jerry P. Eu ◽  
Sarah Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Scaffolding Protein ◽  
Channel Activity ◽  
Skeletal Muscle Function ◽  
Cross Sectional ◽  
Transient Receptor ◽  
Duchenne's Muscular Dystrophy

ABSTRACT Transient receptor potential (TRP) channels are nonselective cation channels, several of which are expressed in striated muscle. Because the scaffolding protein Homer 1 has been implicated in TRP channel regulation, we hypothesized that Homer proteins play a significant role in skeletal muscle function. Mice lacking Homer 1 exhibited a myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. Homer 1 knockout myotubes displayed increased basal current density and spontaneous cation influx. This spontaneous cation influx in Homer 1 knockout myotubes was blocked by reexpression of Homer 1b, but not Homer 1a, and by gene silencing of TRPC1. Moreover, diminished Homer 1 expression in mouse models of Duchenne's muscular dystrophy suggests that loss of Homer 1 scaffolding of TRP channels may contribute to the increased stretch-activated channel activity observed in mdx myofibers. These findings provide direct evidence that Homer 1 functions as an important scaffold for TRP channels and regulates mechanotransduction in skeletal muscle.

scholarly journals Structure of full-length human TRPM4

2018 ◽  
Vol 115 (10) ◽  
pp. 2377-2382 ◽  
Author(s):  
Jingjing Duan ◽  
Zongli Li ◽  
Jian Li ◽  
Ana Santa-Cruz ◽  
Silvia Sanchez-Martinez ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Coiled Coil ◽  
Receptor Potential ◽  
Lipid Binding ◽  
Full Length ◽  
Intramolecular Interactions ◽  
Coiled Coil Domain ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist between the TRP domain and the S4–S5 linker, N-terminal domain, and N and C termini. Finally, we identify aromatic interactions via π–π bonds and cation–π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites. We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.

scholarly journals TRPV4: A Physio and Pathophysiologically Significant Ion Channel

2020 ◽  
Vol 21 (11) ◽  
pp. 3837 ◽  
Author(s):  
Tamara Rosenbaum ◽  
Miguel Benítez-Angeles ◽  
Raúl Sánchez-Hernández ◽  
Sara Luz Morales-Lázaro ◽  
Marcia Hiriart ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Ion Channel ◽  
Therapeutic Target ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor ◽  
Near Future ◽  
Lines Of Evidence

Transient Receptor Potential (TRP) channels are a family of ion channels whose members are distributed among all kinds of animals, from invertebrates to vertebrates. The importance of these molecules is exemplified by the variety of physiological roles they play. Perhaps, the most extensively studied member of this family is the TRPV1 ion channel; nonetheless, the activity of TRPV4 has been associated to several physio and pathophysiological processes, and its dysfunction can lead to severe consequences. Several lines of evidence derived from animal models and even clinical trials in humans highlight TRPV4 as a therapeutic target and as a protein that will receive even more attention in the near future, as will be reviewed here.

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