TY - JOUR
T1 - Endogenous reactive oxygen species modulates voltage-gated sodium channels in dorsal root ganglia of rats
AU - Wang, Han Jun
AU - Li, Yu Long
AU - Zhang, Li Bin
AU - Zucker, Irving H.
AU - Gao, Lie
AU - Zimmerman, Matthew C.
AU - Wang, Wei
N1 - Funding Information:
The authors gratefully acknowledge the financial assistance from Universiti Sains Malaysia (fellowship for Mr Saifullah Ramli) and USM short term grant (304/ PTEKIND/638098).
PY - 2011/5
Y1 - 2011/5
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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U2 - 10.1152/japplphysiol.01409.2010
DO - 10.1152/japplphysiol.01409.2010
M3 - Article
C2 - 21292836
AN - SCOPUS:79956139579
SN - 8750-7587
VL - 110
SP - 1439
EP - 1447
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 5
ER -