scholarly journals Lack of potentiating effect of increasing temperature on responses to chemical activators in vagal sensory neurons isolated from TRPV1-null mice

2008 ◽  
Vol 295 (5) ◽  
pp. L897-L904 ◽  
Author(s):  
Dan Ni ◽  
Lu-Yuan Lee
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Patch Clamp Technique ◽  
Positive Interaction ◽  
Inward Current ◽  
Transient Receptor ◽  
Increasing Temperature

Our recent study (Ni D, Lee LY. Am J Physiol Lung Cell Mol Physiol 294: L563–L571, 2008) demonstrated that the responses of rat pulmonary sensory neurons to transient receptor potential vanilloid (TRPV)1 activators were enhanced by increasing temperature, but the role of the TPRV1 channel in this potentiating effect could not be definitively evaluated. In the present study, we used whole cell perforated patch-clamp technique to compare the responses of isolated nodose/jugular sensory neurons to chemical activators and increasing temperature between wild-type (WT) and TRPV1-null (TRPV1−/−) mice. Our results showed that, in voltage-clamp mode, the peak inward current evoked by hyperthermia was not different between WT and TRPV1−/− neurons; however, the inward current evoked by 2-aminoethoxydiphenyl borate (2-APB), a common activator of TRPV1–3 channels, was greatly potentiated by increasing temperature from 36 to 40.5°C in WT neurons ( n = 9; P < 0.01) but was not affected by the same change in temperature in TRPV1−/− neurons ( n = 9; P = 0.54). Similarly, the inward current evoked by acid (pH 5.5), an activator of both TRPV1 channel and the acid-sensing ion channel, was enhanced by increasing temperature ( n = 7; P < 0.05) in WT neurons, and this potentiating effect was absent in TRPV1−/− neurons ( n = 13; P = 0.11). These results demonstrated that deletion of the TRPV1 channel does not significantly alter the stimulatory effect of hyperthermia on nodose/jugular neurons but eliminates the potentiating effect of increasing temperature on the responses of these neurons to nonselective TRPV1 channel activators. This study further suggests that a positive interaction between these chemical activators and increasing temperature at the TRPV1 channel is primarily responsible for the hyperthermia-induced sensitization of these neurons.

Thermal sensitivity of isolated vagal pulmonary sensory neurons: role of transient receptor potential vanilloid receptors

2006 ◽  
Vol 291 (3) ◽  
pp. R541-R550 ◽  
Author(s):  
Dan Ni ◽  
Qihai Gu ◽  
Hong-Zhen Hu ◽  
Na Gao ◽  
Michael X. Zhu ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Thermal Sensitivity ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Temperature Sensitive ◽  
Inward Current ◽  
Transient Receptor ◽  
Increasing Temperature

A recent study has demonstrated that increasing the intrathoracic temperature from 36°C to 41°C induced a distinct stimulatory and sensitizing effect on vagal pulmonary C-fiber afferents in anesthetized rats ( J Physiol 565: 295–308, 2005). We postulated that these responses are mediated through a direct activation of the temperature-sensitive transient receptor potential vanilloid (TRPV) receptors by hyperthermia. To test this hypothesis, we studied the effect of increasing temperature on pulmonary sensory neurons that were isolated from adult rat nodose/jugular ganglion and identified by retrograde labeling, using the whole cell perforated patch-clamping technique. Our results showed that increasing temperature from 23°C (or 35°C) to 41°C in a ramp pattern evoked an inward current, which began to emerge after exceeding a threshold of ∼34.4°C and then increased sharply in amplitude as the temperature was further increased, reaching a peak current of 173 ± 27 pA ( n = 75) at 41°C. The temperature coefficient, Q10, was 29.5 ± 6.4 over the range of 35–41°C. The peak inward current was only partially blocked by pretreatment with capsazepine (Δ I = 48.1 ± 4.7%, n = 11) or AMG 9810 (Δ I = 59.2 ± 7.8%, n = 8), selective antagonists of the TRPV1 channel, but almost completely abolished (Δ I = 96.3 ± 2.3%) by ruthenium red, an effective blocker of TRPV1–4 channels. Furthermore, positive expressions of TRPV1–4 transcripts and proteins in these neurons were demonstrated by RT-PCR and immunohistochemistry experiments, respectively. On the basis of these results, we conclude that increasing temperature within the normal physiological range can exert a direct stimulatory effect on pulmonary sensory neurons, and this effect is mediated through the activation of TRPV1, as well as other subtypes of TRPV channels.

Effect of increasing temperature on TRPV1-mediated responses in isolated rat pulmonary sensory neurons

2008 ◽  
Vol 294 (3) ◽  
pp. L563-L571 ◽  
Author(s):  
Dan Ni ◽  
Lu-Yuan Lee
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Direct Action ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channel ◽  
Positive Interaction ◽  
C Fibers ◽  
Ganglion Neurons ◽  
Increasing Temperature

Hyperthermia has been shown to sensitize vagal pulmonary C-fibers in anesthetized rats. However, it was not clear whether the effect was due to a direct action of hyperthermia on these sensory neurons. To answer this question, we carried out this study to determine the effect of increasing temperature on the responses to various chemical stimuli in isolated nodose and jugular ganglion neurons innervating the rat lungs. In the whole cell perforated patch-clamp study, when the temperature was increased from normal (∼36°C) to hyperthermic (∼40.6°C) level of the rat body temperature, the inward currents evoked by capsaicin, a selective activator of the transient receptor potential vanilloid type 1 (TRPV1), and 2-aminoethoxydiphenyl borate (2-APB), a nonselective activator of TRPV1–3 receptors, were both significantly increased. This potentiating effect was clearly present even at a moderate level of hyperthermia (∼39°C). However, only the slow, sustained component of acid-evoked current mediated through the TRPV1 receptor was potentiated by hyperthermia, whereas the rapid, transient component was inhibited. In contrast, the currents evoked by adenosine 5′-triphosphate and acetylcholine, neither of which is known to activate the TRPV1 channel, did not increase when the same temperature elevation was applied. Furthermore, the hyperthermia-induced potentiation of the cell response to 2-APB was significantly attenuated by either capsazepine or AMG 9810, selective TRPV1 antagonists. In conclusion, increasing temperature within the physiological range exerts a potentiating effect on the response to TRPV1 activators in these neurons, which is probably mediated through a positive interaction between hyperthermia and these chemical activators at the TRPV1 channel.

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.

scholarly journals Characterization of acid signaling in rat vagal pulmonary sensory neurons

2006 ◽  
Vol 291 (1) ◽  
pp. L58-L65 ◽  
Author(s):  
Qihai Gu ◽  
Lu-Yuan Lee
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Low Ph ◽  
Receptor Subtype ◽  
Transient Receptor Potential Vanilloid ◽  
Inward Current ◽  
Transient Component ◽  
Current Voltage Curve ◽  
Transient Receptor

Local tissue acidosis frequently occurs in airway inflammatory and ischemic conditions. The effect of physiological/pathophysiological-relevant low pH (7.0–5.5) on isolated rat vagal pulmonary sensory neurons was investigated using whole cell perforated patch-clamp recordings. In voltage-clamp recordings, vagal pulmonary sensory neurons exhibited distinct pH sensitivities and different phenotypes of inward current in responding to acidic challenge. The current evoked by lowering the pH of extracellular solution to 7.0 consisted of only a transient, rapidly inactivating component with small amplitude. The amplitude of this transient current increased when the proton concentration was elevated. In addition, a slow, sustained inward current began to emerge when pH was reduced to <6.5. The current-voltage curve indicated that the transient component of acid-evoked current was carried predominantly by Na+. This transient component was dose-dependently inhibited by amiloride, a common blocker of acid-sensing ion channels (ASICs), whereas the sustained component was significantly attenuated by capsazepine, a selective antagonist of transient receptor potential vanilloid receptor subtype-1 (TRPV1). The two components of acid-evoked current also displayed distinct recovery kinetics from desensitization. Furthermore, in current-clamp recordings, transient extracellular acidification depolarized the membrane potential and generated action potentials in these isolated neurons. In summary, our results have demonstrated that low pH can stimulate rat vagal pulmonary sensory neurons through the activation of both ASICs and TRPV1. The relative roles of these two current species depend on the range of pH and vary between neurons.

Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia

2008 ◽  
Vol 294 (5) ◽  
pp. G1288-G1298 ◽  
Author(s):  
Walter E. B. Sipe ◽  
Stuart M. Brierley ◽  
Christopher M. Martin ◽  
Benjamin D. Phillis ◽  
Francisco Bautista Cruz ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Action Potentials ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Mechanical Hyperalgesia ◽  
Transient Receptor Potential Vanilloid ◽  
Afferent Neurons ◽  
Nociceptive Neurons ◽  
Afferent Fibers ◽  
Transient Receptor

Protease-activated receptor (PAR2) is expressed by nociceptive neurons and activated during inflammation by proteases from mast cells, the intestinal lumen, and the circulation. Agonists of PAR2 cause hyperexcitability of intestinal sensory neurons and hyperalgesia to distensive stimuli by unknown mechanisms. We evaluated the role of the transient receptor potential vanilloid 4 (TRPV4) in PAR2-induced mechanical hyperalgesia of the mouse colon. Colonic sensory neurons, identified by retrograde tracing, expressed immunoreactive TRPV4, PAR2, and calcitonin gene-related peptide and are thus implicated in nociception. To assess nociception, visceromotor responses (VMR) to colorectal distension (CRD) were measured by electromyography of abdominal muscles. In TRPV4+/+ mice, intraluminal PAR2 activating peptide (PAR2-AP) exacerbated VMR to graded CRD from 6–24 h, indicative of mechanical hyperalgesia. PAR2-induced hyperalgesia was not observed in TRPV4−/− mice. PAR2-AP evoked discharge of action potentials from colonic afferent neurons in TRPV4+/+ mice, but not from TRPV4−/− mice. The TRPV4 agonists 5′,6′-epoxyeicosatrienoic acid and 4α-phorbol 12,13-didecanoate stimulated discharge of action potentials in colonic afferent fibers and enhanced current responses recorded from retrogradely labeled colonic dorsal root ganglia neurons, confirming expression of functional TRPV4. PAR2-AP enhanced these responses, indicating sensitization of TRPV4. Thus TRPV4 is expressed by primary spinal afferent neurons innervating the colon. Activation of PAR2 increases currents in these neurons, evokes discharge of action potentials from colonic afferent fibers, and induces mechanical hyperalgesia. These responses require the presence of functional TRPV4. Therefore, TRPV4 is required for PAR2-induced mechanical hyperalgesia and excitation of colonic afferent neurons.

scholarly journals Eugenol Inhibits Sodium Currents in Dental Afferent Neurons

2006 ◽  
Vol 85 (10) ◽  
pp. 900-904 ◽  
Author(s):  
C.-K. Park ◽  
H.Y. Li ◽  
K.-Y. Yeon ◽  
S.J. Jung ◽  
S.-Y. Choi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Inhibitory Effect ◽  
Transient Receptor Potential Vanilloid ◽  
Afferent Neurons ◽  
Patch Clamp Technique ◽  
Independent Manner ◽  
Pre Treatment ◽  
Transient Receptor

Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents ( I Na) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and I Na in both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on I Na, suggesting no involvement of TRPV1. Two types of I Na, tetrodotoxin (TTX)-resistant and TTX-sensitive I Na, were inhibited by eugenol. Our results demonstrated that eugenol inhibits I Na in a TRPV1-independent manner. We suggest that I Na inhibition by eugenol contributes to its analgesic effect.

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.

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