본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Effects of Mitochondrial Reactive Oxygen Species on Neuronal Excitability in Rat Spinal Substantia Gelatinosa Neurons

Lee, Hae-In    (Dept. of Oral Physiology, College of Dentistry, Institute of Wonkwang Biomaterial and Implant, Wonkwang University   ); Park, A-Reum    (Dept. of Oral Physiology, College of Dentistry, Institute of Wonkwang Biomaterial and Implant, Wonkwang University   ); Chun, Sang-Woo    (Dept. of Oral Physiology, College of Dentistry, Institute of Wonkwang Biomaterial and Implant, Wonkwang University  );
  • 초록

    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 $100{\mu}M$ 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.


  • 주제어

    electron transport complex .   malate .   succinate .   membrane excitability.  

  • 참고문헌 (30)

    1. Baran CP, Zeigler MM, Tridandapani S, Marsh CB. The role of ROS and RNA in regulating life and death of blood monocytes. Curr Pharm. 2004;10:855-66. 
    2. Bubici C, Papa S, Pham CG, Zazzeroni F, Franzoso G. The NF-kappaB-mediated control of ROS and JNK signaling. Histol Histopathol. 2006;21(1):69-80. 
    3. Djordjevic VB. Free radicals in cell biology. Int Rev Cytol. 2004;237:57-89. 
    4. McGeer EG, McGeer PL. Brain inflammation in Alzheimer disease and the therapeutic implications. Curr Pharm Res. 1999;5:821-36. 
    5. Wells PG, Kim PM, Laposa RR, Nicol CJ, Parman T, Winn LM. Oxidative damage in chemical teratogenesis. Mutat Res. 1997;396:65-78. 
    6. Parman T, Wiley MJ, Wells PG. Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity. Nat Med. 1999;5:582-5. 
    7. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial ROSinduced ROS release: an update and review. Biochim Biophys Acta. 2006;1757(5-6):509-17. 
    8. Kim HY, Chung JM, Chung K. Increased production of mitochondrial superoxide in the spinal cord induces pain behaviors in mice: the effect of mitochondrial electron transport complex inhibitors. Neurosci Lett. 2008;5;447(1): 87-91. 
    9. Stowe DF, Camara AK. Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function. Antioxid Redox Signal. 2009;11(6):1373-414. 
    10. Park ES, Gao X, Chung JM, Chung K. Levels of mitochondrial reactive oxygen species increase in rat neuropathic spinal dorsal horn neurons. Neurosci Lett. 2006; 391:108-11. 
    11. Schwartz ES, Kim HY, Wang J, Lee I, Klann E, Chung JM, Chung K. Persistent pain is dependent on spinal mitochondrial antioxidant levels. J Neurosci. 2008;7;29(1):159-68. 
    12. Kim HK, Park SK, Zhou JL, Taglialatela G, Chung K, Coggeshall RE, Chung JM. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain. 2004;111:116-24. 
    13. Khattab MM. TEMPOL, a membrane-permeable radical scavenger, attenuates peroxynitrite- and superoxide anionenhanced carrageenan-induced paw edema and hyperalgesia: a key role for superoxide anion. Eur J Pharmacol. 2006;548:167-73. 
    14. Lee I, Kim HK, Kim JH, Chung K, Chung JM. The role of reactive oxygen species in capsaicin-induced mechanical hyperalgesia and in the activities of dorsal horn neurons. Pain. 2007;15;133(1-3):9-17. 
    15. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ. Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem. 2003;19;278(38): 36027-31. 
    16. Baines CP. The mitochondrial permeability transition pore and ischemia-reperfusion injury. Basic Res Cardiol. 2009; 104(2):181-8. 
    17. Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL. Mitochondrial dysfunction in cardiac disease: ischemiareperfusion, aging, and heart failure. J Mol Cell Cardiol. 2001;33(6):1065-89. 
    18. Levy D, Zochodne DW. Local nitric oxide synthase activity in a model of neuropathic pain. Eur J Neurosci. 1998;10:1846-55. 
    19. Khalil Z, Khodr B. A role for free radicals and nitric oxide in delayed recovery in aged rats with chronic constriction nerve injury. Free Rad Biol Med. 2001;31:430-9. 
    20. Liu D, Liu J, Sun D, Wen J. The time course of hydroxyl radical formation following spinal cord injury: the possible role of the iron-catalyzed Haber-Weiss reaction. J Neurotrauma. 2004;21:805-16. 
    21. Wang ZQ, Porreca F, Cuzzocrea S, Galen K, Lightfoot R, Masini E. A newly identified role for superoxide in inflammatory pain. J Pharmacol Exp Ther. 2004;309:869-78. 
    22. Gonzalez C, Sanz-Alfayate G, Agapito MT, Gomez-Nino A, Rocher A, Obeso A. Significance of ROS in oxygen sensing in cell systems with sensitivity to physiological hypoxia. Respir Physiol Neurobiol. 2002;132(1):17-41. 
    23. Zoccarato F, Cavallini L, Bortolami S, Alexandre A. Succinate modulation of H2O2 release at NADH: ubiquinone oxidoreductase (Complex I) in brain mitochondria. Biochem J. 2007;406(1):125-9. 
    24. Verkhovskaya ML, Belevich N, Euro L, Wikstrom M, Verkhovsky MI. Real-time electron transfer in respiratory complex I. Proc Natl Acad Sci USA. 2008;105(10):3763-7. 
    25. Hoffman DL, Brookes PS. Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic conditions. J Biol Chem. 2009;284(24):16236-45. 
    26. Turrens JF, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J. 1980;191(2):421-7. 
    27. Han D, Canali R, Rettori D, Kaplowitz N. Effect of glutathione depletion on sites and topology of superoxide and hydrogen peroxide production in mitochondria. Mol Pharmacol. 2003;64(5):1136-44. 
    28. Avshalumov MV, Chen BT, Marshall SP, Pena DM, Rice ME. Glutamate-dependent inhibition of dopamine release in striatum is mediated by a new diffusible messenger, H2O2. J Neurosci. 2003;1;23(7):2744-50. 
    29. Bao L, Avshalumov MV, Rice ME. Partial mitochondrial inhibition causes striatal dopamine release suppression and medium spiny neuron depolarization via H2O2 elevation, not ATP depletion. J Neurosci. 2005;25(43):10029-40. 
    30. Avshalumov MV, Chen BT, Koos T, Rice ME. Endogenous hydrogen peroxide regulates the excitability of midbrain dopamine neurons via ATP-sensitive potassium channels. J Neurosci. 2005;25:4222-31. 

 저자의 다른 논문

  • Lee, Hae-In (5)

    1. 2009 "Actions of Group I Metabotropic Glutamate Receptor Agonist on Synaptic Transmission and Ionic Currents in Rat Medial Vestibular Nucleus Neurons" International journal of oral biology : official journal of the Korean Academy of Oral Biology and the UCLA Dental Research Institute 34 (4): 215~222    
    2. 2010 "Effects of NaOCl on the Intracellular Calcium Concentration in Rat Dorsal Root Ganglion Neurons" International journal of oral biology : official journal of the Korean Academy of Oral Biology and the UCLA Dental Research Institute 35 (3): 129~135    
    3. 2011 "Roles of Metabotropic Glutamate Receptors 1 and 5 in Rat Medial Vestibular Nucleus Neurons" International journal of oral biology : official journal of the Korean Academy of Oral Biology and the UCLA Dental Research Institute 36 (2): 71~78    
    4. 2013 "Effects of NaOCl on Neuronal Excitability and Intracellular Calcium Concentration in Rat Spinal Substantia Gelatinosa Neurons" International journal of oral biology : official journal of the Korean Academy of Oral Biology and the UCLA Dental Research Institute 38 (1): 5~12    
    5. 2014 "Reactive Oxygen Species and Nitrogen Species Differentially Regulate Neuronal Excitability in Rat Spinal Substantia Gelatinosa Neurons" International journal of oral biology : official journal of the Korean Academy of Oral Biology and the UCLA Dental Research Institute 39 (4): 229~236    
  • Park, A-Reum (2)

  • Chun, Sang-Woo (28)

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기