Effects of Mitochondrial Reactive Oxygen Species on Neuronal Excitability in Rat Spinal Substantia Gelatinosa Neurons.
- Author:
Hae In LEE
1
;
A Reum PARK
;
Sang Woo CHUN
Author Information
1. Department of Oral Physiology, College of Dentistry, Institute of Wonkwang Biomaterial and Implant, Wonkwang University, Iksan 570-749, Korea. physio1@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
electron transport complex;
malate;
succinate;
membrane excitability
- MeSH:
Animals;
Antimycin A;
Calcium;
Catalase;
Central Nervous System Sensitization;
Cyclosporine;
Electron Transport;
Fires;
Horns;
Malates;
Membrane Potentials;
Membranes;
Mitochondria;
Neurons;
Nociception;
Permeability;
Rats;
Reactive Oxygen Species;
Rotenone;
Substantia Gelatinosa;
Succinic Acid
- From:International Journal of Oral Biology
2012;37(1):17-23
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Recent studies indicate that reactive oxygen species (ROS) are critically involved in persistent pain primarily through spinal mechanisms, and that mitochondria are the main source of ROS in the spinal dorsal horn. To investigate whether mitochondrial ROS can induce changes in membrane excitability on spinal substantia gelatonosa (SG) neurons, we examined the effects of mitochondrial electron transport complex (ETC) substrates and inhibitors on the membrane potential of SG neurons in spinal slices. Application of ETC inhibitors, rotenone or antimycin A, resulted in a slowly developing and slight membrane depolarization in SG neurons. Also, application of both malate, a complex I substrate, and succinate, a complex II substrate, caused reversible membrane depolarization and enhanced firing activity. Changes in membrane potential after malate exposure were more prominent than succinate exposure. When slices were pretreated with ROS scavengers such as phenyl-N-tert-buthylnitrone (PBN), catalase and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), malate-induced depolarization was significantly decreased. Intracellular calcium above 100 microM increased malateinduced depolarization, witch was suppressed by cyclosporin A, a mitochondrial permeability transition (MPT) inhibitor. These results suggest that enhanced production of spinal mitochondrial ROS can induce nociception through central sensitization.
