scholarly journals Endogenous reactive oxygen species modulates voltage-gated sodium channels in dorsal root ganglia of rats

2011 ◽  
Vol 110 (5) ◽  
pp. 1439-1447 ◽  
Author(s):  
Han-Jun Wang ◽  
Yu-Long Li ◽  
Li-Bin Zhang ◽  
Irving H. Zucker ◽  
Lie Gao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Pressor Response ◽  
Reactive Oxygen ◽  
Muscle Afferents ◽  
Transient Receptor Potential Vanilloid ◽  
Oxygen Species ◽  
Patch Clamp Technique ◽  
Voltage Gated

We recently reported that reactive oxygen species (ROS) plays an excitatory role in modulation of the exercise pressor reflex (EPR) in normal rats. In this study, we further tested two independent hypotheses: 1) ROS interacts with EPR-related ionotropic receptors such as the purinergic receptors (P2) and transient receptor potential vanilloid 1 receptors (TRPV1) to indirectly modulate the EPR function; 2) ROS directly affects excitability of muscle afferents by modulating the voltage-gated sodium (Nav) channels. To test the first hypothesis, we performed animal experiments to investigate the effect of the SOD mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (Tempol) on the pressor response to hindlimb intra-arterial (IA) injection of either α,β-methylene ATP (a P2X agonist) or capsaicin (a TRPV1 agonist) in decerebrate rats. To test the second hypothesis, we used the patch-clamp technique to determine the effect of ROS on Nav channels on the soma of muscle afferents. We also performed local microinjection of a sodium channel blocker, tetrodotoxin (TTX), into ipsilateral L4/L5 dorsal root ganglia (DRGs) to investigate whether the blockade of Nav channels by TTX affects the EPR function. We found that Tempol did not affect the pressor response to injection of either capsaicin or α,β-methylene ATP but significantly decreased the Nav current in small and medium-sized 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled DRG neurons. A membrane-permeant superoxide dismutase, polyethylene glycol (PEG)-SOD, had an effect on the Nav current in these neurons similar to that of Tempol. Microinjection of TTX into L4/L5 DRGs dramatically attenuated the pressor response to static contraction induced by electrical stimulation of L4/L5 ventral roots. These data suggest that ROS modulates the EPR by affecting the activity of the Nav channels on muscle afferents.

scholarly journals A Novel Leg-Shaking Drosophila Mutant Defective in a Voltage-Gated K+ Current and Hypersensitive to Reactive Oxygen Species

2000 ◽  
Vol 20 (16) ◽  
pp. 5958-5964 ◽  
Author(s):  
Jing W. Wang ◽  
James M. Humphreys ◽  
John P. Phillips ◽  
Arthur J. Hilliker ◽  
Chun-Fang Wu
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Voltage Gated ◽  
K Current ◽  
Drosophila Mutant

scholarly journals Extracellular Phosphate Is an Endogenous Regulator for Voltage-Gated Proton Channels and Production of Reactive Oxygen Species in Osteoclasts

2018 ◽  
Vol 114 (3) ◽  
pp. 305a
Author(s):  
Guangshuai Li ◽  
Katsuuki Miura ◽  
Yoshiko Hino ◽  
Yoshie Moriura ◽  
Junko Kawawaki ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Proton Channels ◽  
Voltage Gated ◽  
Endogenous Regulator

scholarly journals Macrophage uptake of oxidized and acetylated low-density lipoproteins and generation of reactive oxygen species are regulated by linear stiffness of the growth surface

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260756
Author(s):  
Erika J. Gruber ◽  
Ali Y. Aygun ◽  
Cynthia A. Leifer
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Expression ◽  
Transient Receptor Potential ◽  
Reactive Oxygen ◽  
Low Density Lipoproteins ◽  
Growth Surface ◽  
Transient Receptor Potential Vanilloid ◽  
Low Density ◽  
Oxygen Species ◽  
Lipid Uptake

Macrophages are key players in the development of atherosclerosis: they scavenge lipid, transform into foam cells, and produce proinflammatory mediators. At the same time, the arterial wall undergoes profound changes in its mechanical properties. We recently showed that macrophage morphology and proinflammatory potential are regulated by the linear stiffness of the growth surface. Here we asked whether linear stiffness also regulates lipid uptake by macrophages. We cultured murine bone marrow-derived macrophages (BMMs) on polyacrylamide gels modeling stiffness of healthy (1kPa) and diseased (10-150kPa) blood vessels. In unprimed BMMs, increased linear stiffness increased uptake of oxidized (oxLDL) and acetylated (acLDL) low density lipoproteins and generation of reactive oxygen species, but did not alter phagocytosis of bacteria or silica particles. Macrophages adapted to stiff growth surfaces had increased mRNA and protein expression of two key lipoprotein receptors: CD36 and scavenger receptor b1. Regulation of the lipoprotein receptor, lectin-like receptor for ox-LDL, was more complex: mRNA expression decreased but surface protein expression increased with increased stiffness. Focal adhesion kinase was required for maximal uptake of oxLDL, but not of acLDL. Uptake of oxLDL and acLDL was independent of rho-associated coiled coil kinase. Through pharmacologic inhibition and genetic deletion, we found that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, plays an inhibitory role in the uptake of acLDL, but not oxLDL. Together, these results implicate mechanical signaling in the uptake of acLDL and oxLDL, opening up the possibility of new pharmacologic targets to modulate lipid uptake by macrophages in vivo.

scholarly journals TRPV1 (Transient Receptor Potential Vanilloid 1) Sensitization of Skeletal Muscle Afferents in Type 2 Diabetic Rats With Hyperglycemia

Hypertension ◽  
2021 ◽  
Author(s):  
Rie Ishizawa ◽  
Han-Kyul Kim ◽  
Norio Hotta ◽  
Gary A. Iwamoto ◽  
Jere H. Mitchell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Muscle Afferents ◽  
Group Iv ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

The blood pressure response to exercise is exaggerated in type 2 diabetes (T2D). However, the underlying mechanisms remain unclear. It is hypothesized that one mechanism mediating the potentiated cardiovascular response in T2D is the sensitization of chemically sensitive afferent neurons by activation of metaboreceptors. To test this hypothesis, we examined TRPV1 (transient receptor potential vanilloid 1)-induced cardiovascular responses in vivo and muscle afferent discharge ex vivo in T2D rats. Additionally, TRPV1 and PKC (protein kinase C) protein levels in dorsal root ganglia subserving skeletal muscle were assessed. For 14 to 16 weeks, Sprague-Dawley rats were given either a normal diet (control) or a high-fat diet in combination with a low dose (35 and 25 mg/kg) of streptozotocin (T2D). Administration of capsaicin, TRPV1 agonist, in hindlimb evoked significantly greater increases in mean arterial pressure and renal sympathetic nerve activity in decerebrated T2D than control. In a muscle-nerve preparation, the discharge to capsaicin exposure in group IV afferents isolated from T2D was likewise significantly augmented at a magnitude that was proportional to glucose concentration. Moreover, the discharge to capsaicin was potentiated by acute exposure of group IV afferents to a high-glucose environment. T2D showed significantly increased phospholyrated-TRPV1 and -PKCα levels in dorsal root ganglia neurons as compared with control. These findings suggest that group IV muscle afferents are sensitized by PKC-induced TRPV1 overactivity in early stage T2D with hyperglycemia and, thereby, may contribute to the potentiated circulatory response to TRPV1 activation in the disease.

scholarly journals Sphingosylphosphorylcholine potentiates vasoreactivity and voltage-gated Ca2+ entry via NOX1 and reactive oxygen species

2015 ◽  
Vol 106 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Yasin Shaifta ◽  
Vladimir A. Snetkov ◽  
Jesus Prieto-Lloret ◽  
Greg A. Knock ◽  
Sergey V. Smirnov ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Voltage Gated
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