scholarly journals Transient Receptor Potential Canonical Channels in Health and Disease: A 2020 Update

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 496
Author(s):  
Priya R. Kirtley ◽  
Gagandeep S. Sooch ◽  
Fletcher A. White ◽  
Alexander G. Obukhov
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Trpc Channels ◽  
Special Issue ◽  
25Th Anniversary ◽  
Trpc Channel ◽  
Transient Receptor Potential Canonical ◽  
Health And Disease ◽  
Transient Receptor

This 2020 Special Issue “TRPC channels” of Cells was dedicated to commemorating the 25th anniversary of discovery of the Transient Receptor Potential Canonical (TRPC) channel subfamily [...]

Regulation of Transient Receptor Potential Canonical 4 Activity by Phospholipase C-δ1

2020 ◽  
Author(s):  
Juyeon Ko ◽  
Jongyun Myeong ◽  
Misun Kwak ◽  
Insuk So
Keyword(s):  
Phospholipase C ◽  
Transient Receptor Potential ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Receptor Potential ◽  
Regulation Mechanism ◽  
Trpc Channels ◽  
Transient Receptor Potential Canonical ◽  
Cell Current ◽  
Transient Receptor

Abstract Transient receptor potential canonical (TRPC) channels are non-selective calcium-permeable cation channels. It is suggested that TRPC4β and TRPC5 channels are regulated by phospholipase C (PLC) signaling, and are especially maintained by phosphatidylinositol 4,5-bisphosphate (PIP2). The PLCδ subtype is the most Ca2+-sensitive form among the isozymes which cleaves phospholipids to respond to the calcium rise. In this study, we investigated the regulation mechanism of TRPC channel by Ca2+, PLCδ1 and PIP2 signaling cascades. The interaction between TRPC4β and PLCδ1 was identified through the Fӧster resonance energy transfer (FRET) and co-immunoprecipitation (Co-IP). With the electrophysiological experiments, we found that TRPC4β-bound PLCδ1 reduces the overall whole-cell current of channel. The Ca2+-via opened channel promotes the activation of PLCδ1, which subsequently decreases PIP2 level. By comparison TRPC4β activity with or without PLCδ1 using differently [Ca2+]i buffered solution, we demonstrated that PLCδ1 functions in normal condition with physiological calcium range. The negative regulation effect of PLCδ1 on TRPC4β helps to elucidate the roles of each PIP2 binding residues whether they are concerned in channel maintenance or inhibition of channel activity.

scholarly journals Structure–Function Relationship and Physiological Roles of Transient Receptor Potential Canonical (TRPC) 4 and 5 Channels

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 73
Author(s):  
Jinsung Kim ◽  
Juyeon Ko ◽  
Chansik Hong ◽  
Insuk So
Keyword(s):  
Ion Channels ◽  
Structure Function ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Trpc Channels ◽  
Transient Receptor Potential Canonical ◽  
Structure Function Relationship ◽  
Transient Receptor ◽  
Function Relationship ◽  
Relationship Of

The study of the structure–function relationship of ion channels has been one of the most challenging goals in contemporary physiology. Revelation of the three-dimensional (3D) structure of ion channels has facilitated our understanding of many of the submolecular mechanisms inside ion channels, such as selective permeability, voltage dependency, agonist binding, and inter-subunit multimerization. Identifying the structure–function relationship of the ion channels is clinically important as well since only such knowledge can imbue potential therapeutics with practical possibilities. In a sense, recent advances in the understanding of the structure–relationship of transient receptor potential canonical (TRPC) channels look promising since human TRPC channels are calcium-permeable, non-selective cation channels expressed in many tissues such as the gastrointestinal (GI) tract, kidney, heart, vasculature, and brain. TRPC channels are known to regulate GI contractility and motility, pulmonary hypertension, right ventricular hypertrophy, podocyte injury, seizure, fear, anxiety-like behavior, and many others. In this article, we tried to elaborate recent findings of Cryo-EM (cryogenic-electron microscopy) based structural information of TRPC 4 and 5 channels and domain-specific functions of the channel, such as G-protein mediated activation mechanism, extracellular modification of the channel, homo/hetero-tetramerization, and pharmacological gating mechanisms.

scholarly journals Transient Receptor Potential Canonical (TRPC) Channels as Modulators of Migration and Invasion

2020 ◽  
Vol 21 (5) ◽  
pp. 1739
Author(s):  
Muhammad Yasir Asghar ◽  
Kid Törnquist
Keyword(s):  
Energy Production ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Migration And Invasion ◽  
Trpc Channels ◽  
Transient Receptor Potential Canonical ◽  
Functional Forms ◽  
Transient Receptor ◽  
Key Events ◽  
In Cells

Calcium (Ca2+) is perhaps the most versatile signaling molecule in cells. Ca2+ regulates a large number of key events in cells, ranging from gene transcription, motility, and contraction, to energy production and channel gating. To accomplish all these different functions, a multitude of channels, pumps, and transporters are necessary. A group of channels participating in these processes is the transient receptor potential (TRP) family of cation channels. These channels are divided into 29 subfamilies, and are differentially expressed in man, rodents, worms, and flies. One of these subfamilies is the transient receptor potential canonical (TRPC) family of channels. This ion channel family comprises of seven isoforms, labeled TRPC1–7. In man, six functional forms are expressed (TRPC1, TRPC3–7), whereas TRPC2 is a pseudogene; thus, not functionally expressed. In this review, we will describe the importance of the TRPC channels and their interacting molecular partners in the etiology of cancer, particularly in regard to regulating migration and invasion.

Pharmacology of TRPC Channels and Its Potential in Cardiovascular and Metabolic Medicine

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Robin S. Bon ◽  
David J. Wright ◽  
David J. Beech ◽  
Piruthivi Sukumar
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Annual Review ◽  
Publication Date ◽  
Trpc Channels ◽  
Trpc Channel ◽  
Channel Inhibition ◽  
Transient Receptor ◽  
Physical And Chemical ◽  
Trpc Proteins

Transient receptor potential canonical (TRPC) proteins assemble to form homo- or heterotetrameric, nonselective cation channels permeable to K+, Na+, and Ca2+. TRPC channels are thought to act as complex integrators of physical and chemical environmental stimuli. Although the understanding of essential physiological roles of TRPC channels is incomplete, their implication in various pathological mechanisms and conditions of the nervous system, kidneys, and cardiovascular system in combination with the lack of major adverse effects of TRPC knockout or TRPC channel inhibition is driving the search of TRPC channel modulators as potential therapeutics. Here, we review the most promising small-molecule TRPC channel modulators, the understanding of their mode of action, and their potential in the study and treatment of cardiovascular and metabolic disease. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Transient Receptor Potential Canonical (TRPC) Channels: Then and Now

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1983
Author(s):  
Xingjuan Chen ◽  
Gagandeep Sooch ◽  
Isaac S. Demaree ◽  
Fletcher A. White ◽  
Alexander G. Obukhov
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Hereditary Diseases ◽  
Trpc Channels ◽  
Dependent Manner ◽  
Transient Receptor Potential Canonical ◽  
Cell Functions ◽  
Transient Receptor

Twenty-five years ago, the first mammalian Transient Receptor Potential Canonical (TRPC) channel was cloned, opening the vast horizon of the TRPC field. Today, we know that there are seven TRPC channels (TRPC1–7). TRPCs exhibit the highest protein sequence similarity to the Drosophila melanogaster TRP channels. Similar to Drosophila TRPs, TRPCs are localized to the plasma membrane and are activated in a G-protein-coupled receptor-phospholipase C-dependent manner. TRPCs may also be stimulated in a store-operated manner, via receptor tyrosine kinases, or by lysophospholipids, hypoosmotic solutions, and mechanical stimuli. Activated TRPCs allow the influx of Ca2+ and monovalent alkali cations into the cytosol of cells, leading to cell depolarization and rising intracellular Ca2+ concentration. TRPCs are involved in the continually growing number of cell functions. Furthermore, mutations in the TRPC6 gene are associated with hereditary diseases, such as focal segmental glomerulosclerosis. The most important recent breakthrough in TRPC research was the solving of cryo-EM structures of TRPC3, TRPC4, TRPC5, and TRPC6. These structural data shed light on the molecular mechanisms underlying TRPCs’ functional properties and propelled the development of new modulators of the channels. This review provides a historical overview of the major advances in the TRPC field focusing on the role of gene knockouts and pharmacological tools.

scholarly journals Emerging Roles of Diacylglycerol-Sensitive TRPC4/5 Channels

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 218 ◽  
Author(s):  
Michael Mederos y Schnitzler ◽  
Thomas Gudermann ◽  
Ursula Storch
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Receptor Activation ◽  
Activation Mechanism ◽  
Regulatory Function ◽  
Cation Channels ◽  
Trpc Channels ◽  
Trpc Channel ◽  
Transient Receptor ◽  
Trpc5 Channels

Transient receptor potential classical or canonical 4 (TRPC4) and TRPC5 channels are members of the classical or canonical transient receptor potential (TRPC) channel family of non-selective cation channels. TRPC4 and TRPC5 channels are widely accepted as receptor-operated cation channels that are activated in a phospholipase C-dependent manner, following the Gq/11 protein-coupled receptor activation. However, their precise activation mechanism has remained largely elusive for a long time, as the TRPC4 and TRPC5 channels were considered as being insensitive to the second messenger diacylglycerol (DAG) in contrast to the other TRPC channels. Recent findings indicate that the C-terminal interactions with the scaffolding proteins Na+/H+ exchanger regulatory factor 1 and 2 (NHERF1 and NHERF2) dynamically regulate the DAG sensitivity of the TRPC4 and TRPC5 channels. Interestingly, the C-terminal NHERF binding suppresses, while the dissociation of NHERF enables, the DAG sensitivity of the TRPC4 and TRPC5 channels. This leads to the assumption that all of the TRPC channels are DAG sensitive. The identification of the regulatory function of the NHERF proteins in the TRPC4/5-NHERF protein complex offers a new starting point to get deeper insights into the molecular basis of TRPC channel activation. Future studies will have to unravel the physiological and pathophysiological functions of this multi-protein channel complex.

scholarly journals Nitric oxide promotes GABA release by activating a voltage-independent Ca2+ influx pathway in retinal amacrine cells

2017 ◽  
Vol 117 (3) ◽  
pp. 1185-1199 ◽  
Author(s):  
J. Wesley Maddox ◽  
Evanna Gleason
Keyword(s):  
Nitric Oxide ◽  
Transient Receptor Potential ◽  
Soluble Guanylate Cyclase ◽  
Receptor Potential ◽  
Amacrine Cells ◽  
Gaba Release ◽  
No Production ◽  
Trpc Channel ◽  
Transient Receptor Potential Canonical ◽  
Transient Receptor

Retinal amacrine cells express nitric oxide (NO) synthase and produce NO, making NO available to regulate the function of amacrine cells. Here we test the hypothesis that NO can alter the GABAergic synaptic output of amacrine cells. We investigate this using whole cell voltage clamp recordings and Ca2+ imaging of cultured chick retinal amacrine cells. When recording from amacrine cells receiving synaptic input from other amacrine cells, we find that NO increases GABAergic spontaneous postsynaptic current (sPSC) frequency. This increase in sPSC frequency does not require the canonical NO receptor, soluble guanylate cyclase, or presynaptic action potentials. However, removal of extracellular Ca2+ and buffering of cytosolic Ca2+ both inhibit the response to NO. In Ca2+ imaging experiments, we confirm that NO increases cytosolic Ca2+ in amacrine cell processes by activating a Ca2+ influx pathway. Neither the increase in sPSC frequency nor the cytosolic Ca2+ elevations are dependent upon Ca2+ release from stores. NO also enhances evoked GABAergic responses. Because voltage-gated Ca2+ channel function is not altered by NO, the increased evoked response is likely due to the combined effect of voltage-dependent Ca2+ influx adding to the NO-dependent, voltage-independent, Ca2+ influx. Insight into the identity of the Ca2+ influx pathway is provided by the transient receptor potential canonical (TRPC) channel inhibitor clemizole, which prevents the NO-dependent increase in sPSC frequency and cytosolic Ca2+ elevations. These data suggest that NO production in the inner retina will enhance Ca2+-dependent GABA release from amacrine cells by activating TRPC channel(s). NEW & NOTEWORTHY Our research provides evidence that nitric oxide (NO) promotes GABAergic output from retinal amacrine cells by activating a likely transient receptor potential canonical-mediated Ca2+ influx pathway. This NO-dependent mechanism promoting GABA release can be voltage independent, suggesting that, in the retina, local NO production can bypass the formal retinal circuitry and increase local inhibition.

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