scholarly journals α1- and α2-Adrenergic responsiveness in human skeletal muscle feed arteries: the role of TRPV ion channels in heat-induced sympatholysis

2014 ◽  
Vol 307 (9) ◽  
pp. H1288-H1297 ◽  
Author(s):  
Jayson R. Gifford ◽  
Stephen J. Ives ◽  
Song-Young Park ◽  
Robert H. I. Andtbacka ◽  
John R. Hyngstrom ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Human Skeletal Muscle ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Temperature Sensitive ◽  
Feed Arteries ◽  
Skeletal Muscle Feed Arteries

The purpose of this study was to determine if heat inhibits α2-adrenergic vasocontraction, similarly to α1-adrenergic contraction, in isolated human skeletal muscle feed arteries (SMFA) and elucidate the role of the temperature-sensitive vanilloid-type transient receptor potential (TRPV) ion channels in this response. Isolated SMFA from 37 subjects were studied using wire myography. α1 [Phenylephrine (PE)]- and α2 [dexmedetomidine (DEX)]-contractions were induced at 37 and 39°C with and without TRPV family and TRPV4-specific inhibition [ruthenium red (RR) and RN-1734, respectively]. Endothelial function [acetylcholine (ACh)] and smooth muscle function [sodium nitroprusside (SNP) and potassium chloride (KCl)] were also assessed under these conditions. Heat and TRPV inhibition was further examined in endothelium-denuded arteries. Contraction data are reported as a percentage of maximal contraction elicited by 100 mM KCl (LTmax). DEX elicited a small and variable contractile response, one-fifth the magnitude of PE, which was not as clearly attenuated when heated from 37 to 39°C (12 ± 4 to 6 ± 2% LTmax; P = 0.18) as were PE-induced contractions (59 ± 5 to 24 ± 4% LTmax; P < 0.05). Both forms of TRPV inhibition restored PE-induced contraction at 39°C (P < 0.05) implicating these channels, particularly the TRPV4 channels, in the heat-induced attenuation of α1-adrenergic vasocontraction. TRPV inhibition significantly blunted ACh relaxation while denudation prevented heat-induced sympatholysis without having an additive effect when combined with TRPV inhibition. In conclusion, physiological increases in temperature elicit a sympatholysis-like inhibition of α1-adrenergic vasocontraction in human SMFA that appears to be mediated by endothelial TRPV4 ion channels.

The Role of TRPV Ion Channels in Heat-induced Sympatholysis of Human Skeletal Muscle Feed Arteries

2014 ◽  
Vol 46 ◽  
pp. 328-329
Author(s):  
Jayson R. Gifford ◽  
Stephen J. Ives ◽  
Song Y. Park ◽  
Robert H.I. Andtbacka ◽  
Joel D. Trinity ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Human Skeletal Muscle ◽  
Feed Arteries ◽  
Skeletal Muscle Feed Arteries

scholarly journals Vasodilatory function in human skeletal muscle feed arteries with advancing age: the role of adropin

2019 ◽  
Vol 597 (7) ◽  
pp. 1791-1804 ◽  
Author(s):  
Oh Sung Kwon ◽  
Robert H. I. Andtbacka ◽  
John R. Hyngstrom ◽  
Russell S. Richardson
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Vasodilatory Function ◽  
Feed Arteries ◽  
Skeletal Muscle Feed Arteries

scholarly journals Heat and α1-adrenergic responsiveness in human skeletal muscle feed arteries: the role of nitric oxide

2012 ◽  
Vol 113 (11) ◽  
pp. 1690-1698 ◽  
Author(s):  
Stephen J. Ives ◽  
Robert H. I. Andtbacka ◽  
Sun Hyung Kwon ◽  
Yan-Ting Shiu ◽  
Ting Ruan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Human Skeletal Muscle ◽  
Bovine Endothelial Cells ◽  
No Bioavailability ◽  
Feed Arteries ◽  
Skeletal Muscle Feed Arteries

Increased local temperature exerts a sympatholytic effect on human skeletal muscle feed arteries. We hypothesized that this attenuated α1-adrenergic receptor responsiveness may be due to a temperature-induced increase in nitric oxide (NO) bioavailability, thereby reducing the impact of the α1-adrenergic receptor agonist phenylephrine (PE). Thirteen human skeletal muscle feed arteries were harvested, and wire myography was used to generate PE concentration-response curves at 37°C and 39°C, with and without the NO synthase (NOS) inhibitor NG-monomethyl-l-arginine (l-NMMA). A subset of arteries ( n = 4) were exposed to 37°C or 39°C, and the protein content of endothelial NOS (eNOS) and α1-adrenergic receptors was determined by Western blot analysis. Additionally, cultured bovine endothelial cells were exposed to static or shear stress conditions at 37°C and 39°C and assayed for eNOS activation (phosphorylation at Ser1177), eNOS expression, and NO metabolites [nitrate + nitrite (NOx)]. Maximal PE-induced vasocontraction (PEmax) was lower at 39°C than at 37°C [39 ± 10 vs. 84 ± 30% maximal response to 100 mM KCl (KClmax)]. NO blockade restored vasocontraction at 39°C to that achieved at 37°C (80 ± 26% KClmax). Western blot analysis of the feed arteries revealed that heating increased eNOS protein, but not α1-adrenergic receptors. Heating of bovine endothelial cells resulted in greater shear stress-induced eNOS activation and NOx production. Together, these data reveal for the first time that, in human skeletal muscle feed arteries, NO blockade can restore the heat-attenuated α1-adrenergic receptor-mediated vasocontraction and implicate endothelium-derived NO bioavailability as a major contributor to heat-induced sympatholysis. Consequently, these findings highlight the important role of vasodilators in modulating the vascular response to vasoconstrictors.

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.

scholarly journals Regulatory switch at the cytoplasmic interface controls TRPV channel gating

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Lejla Zubcevic ◽  
William F Borschel ◽  
Allen L Hsu ◽  
Mario J Borgnia ◽  
Seok-Yong Lee
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Temperature Sensitive ◽  
Physiological Processes ◽  
Physiological Properties ◽  
Electrophysiological Studies ◽  
Transient Receptor ◽  
Large Rearrangements

Temperature-sensitive transient receptor potential vanilloid (thermoTRPV) channels are activated by ligands and heat, and are involved in various physiological processes. ThermoTRPV channels possess a large cytoplasmic ring consisting of N-terminal ankyrin repeat domains (ARD) and C-terminal domains (CTD). The cytoplasmic inter-protomer interface is unique and consists of a CTD coiled around a β-sheet which makes contacts with the neighboring ARD. Despite much existing evidence that the cytoplasmic ring is important for thermoTRPV function, the mechanism by which this unique structure is involved in thermoTRPV gating has not been clear. Here, we present cryo-EM and electrophysiological studies which demonstrate that TRPV3 gating involves large rearrangements at the cytoplasmic inter-protomer interface and that this motion triggers coupling between cytoplasmic and transmembrane domains, priming the channel for opening. Furthermore, our studies unveil the role of this interface in the distinct biophysical and physiological properties of individual thermoTRPV subtypes.

scholarly journals Role of Transient Receptor Potential and Acid-sensing Ion Channels in Peripheral Inflammatory Pain

2010 ◽  
Vol 112 (3) ◽  
pp. 729-741 ◽  
Author(s):  
John P. M. White ◽  
Mario Cibelli ◽  
Antonio Rei Fidalgo ◽  
Cleoper C. Paule ◽  
Faruq Noormohamed ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Ionotropic Receptors ◽  
Acid Sensing Ion Channels ◽  
Peripheral Pain ◽  
Transient Receptor

Pain originating in inflammation is the most common pathologic pain condition encountered by the anesthesiologist whether in the context of surgery, its aftermath, or in the practice of pain medicine. Inflammatory agents, released as components of the body's response to peripheral tissue damage or disease, are now known to be collectively capable of activating transient receptor potential vanilloid type 1, transient receptor potential vanilloid type 4, transient receptor potential ankyrin type 1, and acid-sensing ion channels, whereas individual agents may activate only certain of these ion channels. These ionotropic receptors serve many physiologic functions-as, indeed, do many of the inflammagens released in the inflammatory process. Here, we introduce the reader to the role of these ionotropic receptors in mediating peripheral pain in response to inflammation.

scholarly journals TRPV1channels in human skeletal muscle feed arteries: implications for vascular function

2017 ◽  
Vol 102 (9) ◽  
pp. 1245-1258 ◽  
Author(s):  
Stephen J. Ives ◽  
Song Young Park ◽  
Oh Sung Kwon ◽  
Jayson R. Gifford ◽  
Robert H. I. Andtbacka ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vascular Function ◽  
Human Skeletal Muscle ◽  
Feed Arteries ◽  
Skeletal Muscle Feed Arteries

scholarly journals Evidence of the regulatory potential of human skeletal muscle feed arteries

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Stephen James Ives ◽  
Robert Hans Ingemar Andtbacka ◽  
R. Dirk Noyes ◽  
Anthony Donato ◽  
Song Young Park ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Regulatory Potential ◽  
Feed Arteries ◽  
Skeletal Muscle Feed Arteries
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