A Transient Receptor Potential Ion Channel in Chlamydomonas Shares Key Features with Sensory Transduction-Associated TRP Channels in Mammals

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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The push-to-open mechanism of the tethered mechanosensitive ion channel NompC

eLife ◽

10.7554/elife.58388 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yang Wang ◽

Yifeng Guo ◽

Guanluan Li ◽

Chunhong Liu ◽

Lei Wang ◽

...

Keyword(s):

Ion Channel ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Ankyrin Repeat ◽

Gating Mechanism ◽

Repeat Domain ◽

Mechanosensitive Ion Channel ◽

Transient Receptor ◽

Dynamics Simulations

NompC is a mechanosensitive ion channel responsible for the sensation of touch and balance in Drosophila melanogaster. Based on a resolved cryo-EM structure, we performed all-atom molecular dynamics simulations and electrophysiological experiments to study the atomistic details of NompC gating. Our results showed that NompC could be opened by compression of the intracellular ankyrin repeat domain but not by a stretch, and a number of hydrogen bonds along the force convey pathway are important for the mechanosensitivity. Under intracellular compression, the bundled ankyrin repeat region acts like a spring with a spring constant of ~13 pN nm−1 by transferring forces at a rate of ~1.8 nm ps−1. The linker helix region acts as a bridge between the ankyrin repeats and the transient receptor potential (TRP) domain, which passes on the pushing force to the TRP domain to undergo a clockwise rotation, resulting in the opening of the channel. This could be the universal gating mechanism of similar tethered mechanosensitive TRP channels, which enable cells to feel compression and shrinkage.

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Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00401.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. G635-G648 ◽

Cited By ~ 27

Author(s):

Dafne Balemans ◽

Guy E. Boeckxstaens ◽

Karel Talavera ◽

Mira M. Wouters

Keyword(s):

Signaling Pathways ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Visceral Hypersensitivity ◽

Sensory Transduction ◽

Trp Channel ◽

Visceral Afferents ◽

Altered Expression ◽

Transient Receptor

Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders including functional dyspepsia, irritable bowel syndrome, and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM5, and TRPM8), and modulation of their function by increased activation or sensitization (decreased activation threshold) or altered expression in visceral afferents have been reported in visceral hypersensitivity. TRP channels directly detect or transduce osmotic, mechanical, thermal, and chemosensory stimuli. In addition, pro-inflammatory mediators released in tissue damage or inflammation can activate receptors of the G protein-coupled receptor superfamily leading to TRP channel sensitization and activation, which amplify pain and neurogenic inflammation. In this review, we highlight the present knowledge on the functional roles of neuronal TRP channels in visceral hypersensitivity and discuss the signaling pathways that underlie TRP channel modulation. We propose that a better understanding of TRP channels and their modulators may facilitate the development of more selective and effective therapies to treat visceral hypersensitivity.

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Expression of Transient Receptor Potential Ankyrin 1 and Transient Receptor Potential Vanilloid 1 in the Gut of the Peri-Weaning Pig Is Strongly Dependent on Age and Intestinal Site

Animals ◽

10.3390/ani10122417 ◽

2020 ◽

Vol 10 (12) ◽

pp. 2417

Author(s):

Elout Van Liefferinge ◽

Noémie Van Noten ◽

Jeroen Degroote ◽

Gunther Vrolix ◽

Mario Van Poucke ◽

...

Keyword(s):

Small Intestine ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

The Body ◽

Enteroendocrine Cells ◽

Sensory Transduction ◽

Transient Receptor Potential Vanilloid ◽

Distal Small Intestine ◽

Transient Receptor

Transient receptor potential (TRP) channels contribute to sensory transduction in the body, agonized by a variety of stimuli, such as phytochemicals, and they are predominantly distributed in afferent neurons. Evidence indicates their expression in non-neuronal cells, demonstrating their ability to modulate gastrointestinal function. Targeting TRP channels could potentially be used to regulate gastrointestinal secretion and motility, yet their expression in the pig is unknown. This study investigated TRPA1 and TRPV1 expression in different gut locations of piglets of varying age. Colocalization with enteroendocrine cells was established by immunohistochemistry. Both channels were expressed in the gut mucosa. TRPV1 mRNA abundance increased gradually in the stomach and small intestine with age, most notably in the distal small intestine. In contrast, TRPA1 exhibited sustained expression across ages and locations, with the exception of higher expression in the pylorus at weaning. Immunohistochemistry confirmed the endocrine nature of both channels, showing the highest frequency of colocalization in enteroendocrine cells for TRPA1. Specific co-localization on GLP-1 immunoreactive cells indicated their possible role in GLP-1 release and the concomitant intestinal feedback mechanism. Our results indicate that TRPA1 and TRPV1 could play a role in gut enteroendocrine activity. Moreover, age and location in the gut significantly affected gene expression.

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

The Journal of General Physiology ◽

10.1085/jgp.201411336 ◽

2015 ◽

Vol 146 (1) ◽

pp. 65-77 ◽

Cited By ~ 38

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.

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Unitary Recordings of TRP and TRPL Channels From Isolated Drosophila Retinal Photoreceptor Rhabdomeres: Activation by Light and Lipids

Journal of Neurophysiology ◽

10.1152/jn.90578.2008 ◽

2009 ◽

Vol 101 (5) ◽

pp. 2372-2379 ◽

Cited By ~ 24

Author(s):

Ricardo Delgado ◽

Juan Bacigalupo

Keyword(s):

Fatty Acids ◽

Transient Receptor Potential ◽

Trp Channels ◽

Single Channel ◽

Receptor Potential ◽

Sensory Transduction ◽

Retinal Photoreceptor ◽

Dependent Activity ◽

Voltage Dependent ◽

Transient Receptor

Transient receptor potential (TRP) channels play key roles in sensory transduction. The TRP family founding members, the Drosophila light-dependent channels, were previously studied under voltage clamp, but had not been characterized in intact rhabdomeres at single-channel level. We report patch-clamp recordings from intact isolated photoreceptors of wt and mutant flies lacking TRP ( trp 343), TRPL ( trpl 302), or both channels ( trp 313 ; trpl 302). Unitary currents were activated by light in rhabdomere-attached patches. In excised rhabdomeral patches, the channels were directly activated by molecules implicated in phototransduction, such as diacylglycerol and polyunsaturated fatty acids. Currents recorded from trpl photoreceptors are blocked by external Ca2+, Mg2+ (1 mM), and La3+ (20 μM), whereas those from trp photoreceptors are not. Rhabdomeric patches lacked voltage-dependent activity. Patches from trp;trpl mutants were devoid of channels. These characteristics match the macroscopic conductances, suggesting that the unitary currents from Drosophila trpl and trp photoreceptors correspond to TRP and TRPL.

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Structure of the mammalian TRPM7, a magnesium channel required during embryonic development

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1810719115 ◽

2018 ◽

Vol 115 (35) ◽

pp. E8201-E8210 ◽

Cited By ~ 45

Author(s):

Jingjing Duan ◽

Zongli Li ◽

Jian Li ◽

Raymond E. Hulse ◽

Ana Santa-Cruz ◽

...

Keyword(s):

Embryonic Development ◽

Ion Channel ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Ion Binding ◽

Nonselective Cation Channel ◽

Structural Framework ◽

Transient Receptor ◽

Key Residues

The transient receptor potential ion channel subfamily M, member 7 (TRPM7), is a ubiquitously expressed protein that is required for mouse embryonic development. TRPM7 contains both an ion channel and an α-kinase. The channel domain comprises a nonselective cation channel with notable permeability to Mg2+ and Zn2+. Here, we report the closed state structures of the mouse TRPM7 channel domain in three different ionic conditions to overall resolutions of 3.3, 3.7, and 4.1 Å. The structures reveal key residues for an ion binding site in the selectivity filter, with proposed partially hydrated Mg2+ ions occupying the center of the conduction pore. In high [Mg2+], a prominent external disulfide bond is found in the pore helix, which is essential for ion channel function. Our results provide a structural framework for understanding the TRPM1/3/6/7 subfamily and extend the knowledge base upon which to study the diversity and evolution of TRP channels.

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