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

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Abstract

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 (P 2) 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 membranepermeant 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.

Original languageEnglish (US)
Pages (from-to)1439-1447
Number of pages9
JournalJournal of Applied Physiology
Volume110
Issue number5
DOIs
StatePublished - May 1 2011

Fingerprint

Voltage-Gated Sodium Channels
Spinal Ganglia
Reflex
Reactive Oxygen Species
Tetrodotoxin
Capsaicin
Microinjections
Muscles
Adenosine Triphosphate
Sodium Channel Blockers
Intra-Arterial Injections
Neurons
Purinergic Receptors
Spinal Nerve Roots
Carisoprodol
Patch-Clamp Techniques
Hindlimb
Electric Stimulation
Injections
2,2,6,6-tetramethyl-1-piperidine

Keywords

  • Exercise
  • Free radicals
  • Ion channels
  • Muscle afferents

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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title = "Endogenous reactive oxygen species modulates voltage-gated sodium channels in dorsal root ganglia of rats",
abstract = "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 (P 2) 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 membranepermeant 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.",
keywords = "Exercise, Free radicals, Ion channels, Muscle afferents",
author = "Hanjun Wang and Yulong Li and Zhang, {Li Bin} and Zucker, {Irving H} and Lie Gao and Zimmerman, {Matthew C} and Wei Wang",
year = "2011",
month = "5",
day = "1",
doi = "10.1152/japplphysiol.01409.2010",
language = "English (US)",
volume = "110",
pages = "1439--1447",
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TY - JOUR

T1 - Endogenous reactive oxygen species modulates voltage-gated sodium channels in dorsal root ganglia of rats

AU - Wang, Hanjun

AU - Li, Yulong

AU - Zhang, Li Bin

AU - Zucker, Irving H

AU - Gao, Lie

AU - Zimmerman, Matthew C

AU - Wang, Wei

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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 (P 2) 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 membranepermeant 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.

AB - 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 (P 2) 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 membranepermeant 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.

KW - Exercise

KW - Free radicals

KW - Ion channels

KW - Muscle afferents

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VL - 110

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JO - Journal of Applied Physiology

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