scholarly journals TRPV1: Structure, Endogenous Agonists, and Mechanisms

2020 ◽  
Vol 21 (10) ◽  
pp. 3421 ◽  
Author(s):  
Miguel Benítez-Angeles ◽  
Sara Luz Morales-Lázaro ◽  
Emmanuel Juárez-González ◽  
Tamara Rosenbaum
Keyword(s):  
Ion Channel ◽  
Binding Sites ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Field Of Study ◽  
Transient Receptor ◽  
Shed Light ◽  
Made In

The Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a polymodal protein with functions widely linked to the generation of pain. Several agonists of exogenous and endogenous nature have been described for this ion channel. Nonetheless, detailed mechanisms and description of binding sites have been resolved only for a few endogenous agonists. This review focuses on summarizing discoveries made in this particular field of study and highlighting the fact that studying the molecular details of activation of the channel by different agonists can shed light on biophysical traits that had not been previously demonstrated.

scholarly journals Phosphoinositides regulate the TRPV1 channel via two functionally distinct binding sites

2019 ◽  
Author(s):  
Aysenur Torun Yazici ◽  
Eleonora Gianti ◽  
Marina A. Kasimova ◽  
Vincenzo Carnevale ◽  
Tibor Rohacs
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Distinct Site ◽  
Excised Patches ◽  
Transient Receptor ◽  
Dynamics Simulations

AbstractRegulation of the heat- and capsaicin-activated Transient Receptor Potential Vanilloid 1 (TRPV1) channel by phosphoinositides is controversial. In a recent cryoEM structure, an endogenous phosphoinositide was detected in the vanilloid binding site, and phosphoinositides were proposed to act as competitive vanilloid antagonists. This model is difficult to reconcile with phosphatidylinositol 4,5- bisphosphate [PtdIns(4,5)P2] being a well established positive regulator of TRPV1. To resolve this controversy, we propose that phosphoinositides regulate TRPV1 via two functionally distinct binding sites. Our molecular dynamics simulations show that phosphatidylinositol (PtdIns) is more stable in the vanilloid binding site, whereas a distinct site responsible for activation is preferentially occupied by PtdIns(4,5)P2. Consistently, we show that in the presence of PtdIns(4,5)P2 in excised patches PtdIns partially inhibited TRPV1 activity induced by low, but not high capsaicin concentrations. In the absence of PtdIns(4,5)P2 on the other hand, PtdIns partially stimulated TRPV1 activity presumably by binding to the activating site. Overall, our data resolve a major controversy in the regulation of TRPV1.

scholarly journals Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Muhammad Azhar Sherkheli ◽  
Guenter Gisselmann ◽  
Hanns Hatt
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Human Keratinocytes ◽  
Transient Receptor Potential Vanilloid ◽  
Neural Cells ◽  
Hek 293 ◽  
Low Concentrations ◽  
293 Cells ◽  
Transient Receptor

Transient receptor potential vanilloid subtype 3 (TRPV3) is a thermosensitive ion channel expressed in a variety of neural cells and in keratinocytes. It is activated by warmth (33–39°C), and its responsiveness is dramatically increased at nociceptive temperatures greater than 40°C. Monoterpenoids and 2-APB are chemical activators of TRPV3 channels. We found that Icilin, a known cooling substance and putative ligand of TRPM8, reversibly inhibits TRPV3 activity at nanomolar concentrations in expression systems likeXenopus laevesoocytes, HEK-293 cells, and in cultured human keratinocytes. Our data show that icilin's antagonistic effects for the warm-sensitive TRPV3 ion channel occurs at very low concentrations. Therefore, the cooling effect evoked by icilin may at least in part be due to TRPV3 inhibition in addition to TRPM8 potentiation. Blockade of TRPV3 activity by icilin at such low concentrations might have important implications for overall cooling sensations detected by keratinocytes and free nerve endings in skin. We hypothesize that blockage of TRPV3 might be a signal for cool-sensing systems (like TRPM8) to beat up the basal activity resulting in increased cold perception when warmth sensors (like TRPV3) are shut off.

scholarly journals Pore Helix Domain Is Critical to Camphor Sensitivity of Transient Receptor Potential Vanilloid 1 Channel

2012 ◽  
Vol 116 (4) ◽  
pp. 903-917 ◽  
Author(s):  
Lenka Marsakova ◽  
Filip Touska ◽  
Jan Krusek ◽  
Viktorie Vlachova
Keyword(s):  
Spatial Distribution ◽  
Plasma Membranes ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Structural Basis ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Patch Clamp Technique ◽  
Trpv1 Channels ◽  
Transient Receptor

Background The recent discovery that camphor activates and strongly desensitizes the capsaicin-sensitive and noxious heat-sensitive channel transient receptor potential vanilloid subfamily member 1 (TRPV1) has provided new insights and opened up new research paths toward understanding why this naturally occurring monoterpene is widely used in human medicine for its local counter-irritant, antipruritic, and anesthetic properties. However, the molecular basis for camphor sensitivity remains mostly unknown. The authors attempt to explore the nature of the activation pathways evoked by camphor and narrow down a putative interaction site at TRPV1. Methods The authors transiently expressed wild-type or specifically mutated recombinant TRPV1 channels in human embryonic kidney cells HEK293T and recorded cation currents with the whole cell, patch clamp technique. To monitor changes in the spatial distribution of phosphatidylinositol 4,5-bisphosphate, they used fluorescence resonance energy transfer measurements from cells transfected with the fluorescent protein-tagged pleckstrin homology domains of phospholipase C. Results The results revealed that camphor modulates TRPV1 channel through the outer pore helix domain by affecting its overall gating equilibrium. In addition, camphor, which generally is known to decrease the fluidity of cell plasma membranes, may also regulate the activity of TRPV1 by inducing changes in the spatial distribution of phosphatidylinositol-4,5-bisphosphate on the inner leaflet of the plasma membrane. Conclusions The findings of this study provide novel insights into the structural basis for the modulation of TRPV1 channel by camphor and may provide an explanation for the mechanism by which camphor modulates thermal sensation in vivo.

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