scholarly journals Ion Channels and Thermosensitivity: TRP, TREK, or Both?

2019 ◽  
Vol 20 (10) ◽  
pp. 2371 ◽  
Author(s):  
J. Antonio Lamas ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Body Temperature ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Wide Range ◽  
Cold Receptors ◽  
Thermoregulatory System ◽  
Transient Receptor

Controlling body temperature is a matter of life or death for most animals, and in mammals the complex thermoregulatory system is comprised of thermoreceptors, thermosensors, and effectors. The activity of thermoreceptors and thermoeffectors has been studied for many years, yet only recently have we begun to obtain a clear picture of the thermosensors and the molecular mechanisms involved in thermosensory reception. An important step in this direction was the discovery of the thermosensitive transient receptor potential (TRP) cationic channels, some of which are activated by increases in temperature and others by a drop in temperature, potentially converting the cells in which they are expressed into heat and cold receptors. More recently, the TWIK-related potassium (TREK) channels were seen to be strongly activated by increases in temperature. Hence, in this review we want to assess the hypothesis that both these groups of channels can collaborate, possibly along with other channels, to generate the wide range of thermal sensations that the nervous system is capable of handling.

Transient receptor potential ion channels as participants in thermosensation and thermoregulation

2007 ◽  
Vol 292 (1) ◽  
pp. R64-R76 ◽  
Author(s):  
Michael J. Caterina
Keyword(s):  
Ion Channels ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Core Body Temperature ◽  
Expression Patterns ◽  
Receptor Potential ◽  
Genetic Ablation ◽  
Transient Receptor ◽  
Living Organisms

Living organisms must evaluate changes in environmental and internal temperatures to mount appropriate physiological and behavioral responses conducive to survival. Classical physiology has provided a wealth of information regarding the specialization of thermosensory functions among subclasses of peripheral sensory neurons and intrinsically thermosensitive neurons within the hypothalamus. However, until recently, the molecular mechanisms by which these cells carry out thermometry have remained poorly understood. The demonstration that certain ion channels of the transient receptor potential (TRP) family can be activated by increases or decreases in ambient temperature, along with the recognition of their heterogeneous expression patterns and heterogeneous temperature sensitivities, has led investigators to evaluate these proteins as candidate endogenous thermosensors. Much of this work has involved one specific channel, TRP vanilloid 1 (TRPV1), which is both a receptor for capsaicin and related pungent vanilloid compounds and a “heat receptor,” capable of directly depolarizing neurons in response to temperatures >42°C. Evidence for a contribution of TRPV1 to peripheral thermosensation has come from pharmacological, physiological, and genetic approaches. In contrast, although capsaicin-sensitive mechanisms clearly influence core body temperature regulation, the specific contribution of TRPV1 to this process remains a matter of debate. Besides TRPV1, at least six additional thermally sensitive TRP channels have been identified in mammals, and many of these also appear to participate in thermosensation. Moreover, the identification of invertebrate TRP channels, whose genetic ablation alters thermally driven behaviors, makes it clear that thermosensation represents an evolutionarily conserved role of this ion channel family.

scholarly journals Role of lysophosphatidic acid in ion channel function and disease

2018 ◽  
Vol 120 (3) ◽  
pp. 1198-1211 ◽  
Author(s):  
Ileana Hernández-Araiza ◽  
Sara L. Morales-Lázaro ◽  
Jesús Aldair Canul-Sánchez ◽  
León D. Islas ◽  
Tamara Rosenbaum
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Lysophosphatidic Acid ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Channel Function ◽  
Transient Receptor ◽  
Lipid Protein Interactions

Lysophosphatidic acid (LPA) is a bioactive phospholipid that exhibits a wide array of functions that include regulation of protein synthesis and adequate development of organisms. LPA is present in the membranes of cells and in the serum of several mammals and has also been shown to participate importantly in pathophysiological conditions. For several decades it was known that LPA produces some of its effects in cells through its interaction with specific G protein-coupled receptors, which in turn are responsible for signaling pathways that regulate cellular function. Among the target proteins for LPA receptors are ion channels that modulate diverse aspects of the physiology of cells and organs where they are expressed. However, recent studies have begun to unveil direct effects of LPA on ion channels, highlighting this phospholipid as a direct agonist and adding to the knowledge of the field of lipid-protein interactions. Moreover, the roles of LPA in pathophysiological conditions associated with the function of some ion channels have also begun to be clarified, and molecular mechanisms have been identified. This review focuses on the effects of LPA on ion channel function under normal and pathological conditions and highlights our present knowledge of the mechanisms by which it regulates the function and expression of N- and T-type Ca++ channels; M-type K+ channel and inward rectifier K+ channel subunit 2.1; transient receptor potential (TRP) melastatin 2, TRP vanilloid 1, and TRP ankyrin 1 channels; and TWIK-related K+ channel 1 (TREK-1), TREK-2, TWIK-related spinal cord K+ channel (TRESK), and TWIK-related arachidonic acid-stimulated K+ channel (TRAAK).

scholarly journals TRPM7 and TRPM8 Ion Channels in Pancreatic Adenocarcinoma: Potential Roles as Cancer Biomarkers and Targets

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Nelson S. Yee ◽  
Ada S. Chan ◽  
Julian D. Yee ◽  
Rosemary K. Yee
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Molecular Sensors ◽  
Functional Roles ◽  
Normal Functions ◽  
Clinical Biomarkers ◽  
Trp Ion Channels ◽  
Wide Range ◽  
Transient Receptor

Transient receptor potential (TRP) ion channels are essential for normal functions and health by acting as molecular sensors and transducing various stimuli into cellular and physiological responses. Growing evidence has revealed that TRP ion channels play important roles in a wide range of human diseases, including malignancies. In light of recent discoveries, it has been found that TRP melastatin-subfamily members, TRPM7 and TRPM8, are required for normal and cancerous development of exocrine pancreas. We are currently investigating the mechanisms which mediate the functional roles of TRPM7 and TRPM8 and attempting to develop these ion channels as clinical biomarkers and therapeutic targets for achieving the goal of personalized therapy in pancreatic cancer.

scholarly journals Emerging Role of Transient Receptor Potential Vanilloid 4 (TRPV4) Ion Channel in Acute and Chronic Itch

2021 ◽  
Vol 22 (14) ◽  
pp. 7591
Author(s):  
Qiaojuan Zhang ◽  
Gwendolyn Henry ◽  
Yong Chen
Keyword(s):  
Ion Channels ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Clinical Problem ◽  
The United States ◽  
Transient Receptor Potential Vanilloid ◽  
Research Attention ◽  
Chronic Itch ◽  
Transient Receptor

Itch is a clinical problem that leaves many sufferers insufficiently treated, with over 20 million cases in the United States. This is due to incomplete understanding of its molecular, cellular, and cell-to-cell signaling mechanisms. Transient receptor potential (TRP) ion channels are involved in several sensory modalities including pain, vision, taste, olfaction, hearing, touch, and thermosensation, as well as itch. Relative to the extensive studies on TRPV1 and TRPA1 ion channels in itch modulation, TRPV4 has received relatively little research attention and its mechanisms have remained poorly understood until recently. TRPV4 is expressed in ganglion sensory neurons and a variety of skin cells. Growing evidence in the past few years strongly suggests that TRPV4 in these cells contributes to acute and chronic disease-associated itch. This review focuses on the current experimental evidence involving TRPV4 in itch under pathophysiological conditions and discusses its possible cellular and molecular mechanisms.

scholarly journals Structural mechanisms of transient receptor potential ion channels

2020 ◽  
Vol 152 (3) ◽  
Author(s):  
Erhu Cao
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Wide Range ◽  
Human Disorders ◽  
Transient Receptor ◽  
Voltage Gated Ion Channels ◽  
Structural Mechanisms ◽  
Physical And Chemical

Transient receptor potential (TRP) ion channels are evolutionarily ancient sensory proteins that detect and integrate a wide range of physical and chemical stimuli. TRP channels are fundamental for numerous biological processes and are therefore associated with a multitude of inherited and acquired human disorders. In contrast to many other major ion channel families, high-resolution structures of TRP channels were not available before 2013. Remarkably, however, the subsequent “resolution revolution” in cryo-EM has led to an explosion of TRP structures in the last few years. These structures have confirmed that TRP channels assemble as tetramers and resemble voltage-gated ion channels in their overall architecture. But beyond the relatively conserved transmembrane core embedded within the lipid bilayer, each TRP subtype appears to be endowed with a unique set of soluble domains that may confer diverse regulatory mechanisms. Importantly, TRP channel TR structures have revealed sites and mechanisms of action of numerous synthetic and natural compounds, as well as those for endogenous ligands such as lipids, Ca2+, and calmodulin. Here, I discuss these recent findings with a particular focus on the conserved transmembrane region and how these structures may help to rationally target this important class of ion channels for the treatment of numerous human conditions.

scholarly journals Electrophysiological and Molecular Mechanisms of Sinoatrial Node Mechanosensitivity

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniel Turner ◽  
Chen Kang ◽  
Pietro Mesirca ◽  
Juan Hong ◽  
Matteo E. Mangoni ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Ion Channels ◽  
Chloride Channels ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Sinoatrial Node ◽  
Receptor Potential ◽  
Past Century ◽  
Transient Receptor

The understanding of the electrophysiological mechanisms that underlie mechanosensitivity of the sinoatrial node (SAN), the primary pacemaker of the heart, has been evolving over the past century. The heart is constantly exposed to a dynamic mechanical environment; as such, the SAN has numerous canonical and emerging mechanosensitive ion channels and signaling pathways that govern its ability to respond to both fast (within second or on beat-to-beat manner) and slow (minutes) timescales. This review summarizes the effects of mechanical loading on the SAN activity and reviews putative candidates, including fast mechanoactivated channels (Piezo, TREK, and BK) and slow mechanoresponsive ion channels [including volume-regulated chloride channels and transient receptor potential (TRP)], as well as the components of mechanochemical signal transduction, which may contribute to SAN mechanosensitivity. Furthermore, we examine the structural foundation for both mechano-electrical and mechanochemical signal transduction and discuss the role of specialized membrane nanodomains, namely, caveolae, in mechanical regulation of both membrane and calcium clock components of the so-called coupled-clock pacemaker system responsible for SAN automaticity. Finally, we emphasize how these mechanically activated changes contribute to the pathophysiology of SAN dysfunction and discuss controversial areas necessitating future investigations. Though the exact mechanisms of SAN mechanosensitivity are currently unknown, identification of such components, their impact into SAN pacemaking, and pathological remodeling may provide new therapeutic targets for the treatment of SAN dysfunction and associated rhythm abnormalities.

The Transient Receptor Potential Vanilloid Type 1 Ion Channel in Hypometabolic Response to Hypoxia

2018 ◽  
Author(s):  
Brian Foo
Keyword(s):  
Body Temperature ◽  
Ion Channel ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Receptor ◽  
Transient Receptor ◽  
Knockout Animals

When challenged with low levels of available oxygen (hypoxia), larger mammals, including humans, attempt to maintain a consistent oxygen supply by increasing their rate of respiration. Smaller rodents and newborn mammals, on the other hand, respond to hypoxia by curtailing oxygen consumption. This latter process (hypoxic hypometabolism) involves actively regulated reductions in both metabolic rate and body temperature (3; 4; 9). Despite more than 50 years of investigation, the molecular mechanisms of this intriguing process are still unclear. Recently, the transient receptor potential vanilloid type 1 (TRPV1) receptor (best known for its response to capsaicin) has been implicated in the regulation of body temperature (5). Evidence includes the ability of TRPV1 receptor agonists and antagonists to lower and raise body temperature respectively (6; 7), as well as a demonstrated site of action within thehypothalamus (the area of the brain responsible for the regulation of body temperature) (1; 2). Based on the parallel but separately identified roles of hypoxia and TRPV1 in controlling body temperature, we reasoned that the TRPV1 ion channel may be implicated in hypoxia-induced alterations in body temperature. This present study investigates the potential involvement of the TRPV1 ion channel in hypoxia mediated hypothermia by comparing the hypoxic responses of wild-type mice and transgenetic knockout animals lacking a functional TRPV1 gene. We hypothesize that the TRPV1 knockout animals will show a blunted hypothermic response to hypoxic challenge. 

scholarly journals The transient receptor potential, TRP4, cation channel is a novel member of the family of calmodulin binding proteins

2001 ◽  
Vol 355 (3) ◽  
pp. 663-670 ◽  
Author(s):  
Claudia TROST ◽  
Christiane BERGS ◽  
Nina HIMMERKUS ◽  
Veit FLOCKERZI
Keyword(s):  
Amino Acid ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Direct Interaction ◽  
Receptor Potential ◽  
Amino Acid Residues ◽  
Glutathione S Transferase ◽  
Calmodulin Binding ◽  
Transient Receptor

The mammalian gene products, transient receptor potential (trp)1 to trp7, are related to the Drosophila TRP and TRP-like ion channels, and are candidate proteins underlying agonist-activated Ca2+-permeable ion channels. Recently, the TRP4 protein has been shown to be part of native store-operated Ca2+-permeable channels. These channels, most likely, are composed of other proteins in addition to TRP4. In the present paper we report the direct interaction of TRP4 and calmodulin (CaM) by: (1) retention of in vitro translated TRP4 and of TRP4 protein solubilized from bovine adrenal cortex by CaM–Sepharose in the presence of Ca2+, and (2) TRP4–glutathione S-transferase pull-down experiments. Two domains of TRP4, amino acid residues 688–759 and 786–848, were identified as being able to interact with CaM. The binding of CaM to both domains occurred only in the presence of Ca2+ concentrations above 10µM, with half maximal binding occurring at 16.6µM (domain 1) and 27.9µM Ca2+ (domain 2). Synthetic peptides, encompassing the two putative CaM binding sites within these domains and covering amino acid residues 694–728 and 829–853, interacted directly with dansyl–CaM with apparent Kd values of 94–189nM. These results indicate that TRP4/Ca2+-CaM are parts of a signalling complex involved in agonist-induced Ca2+ entry.

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