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Genel Anesteziklerin Moleküler Mekanizması

Yıl 2020, Cilt 10, Sayı 3, 140 - 143, 24.12.2020
https://doi.org/10.26650/experimed.2020.824840

Öz

Genel anestezik ajanlar, nörotransmitterleri modüle ederek santral sinir sisteminde yaygın nöronal değişime neden olmaktadır. Yeni yapılan moleküler araştırmalarda anestezik ajanların etki ettiği spesifik alanlar üzerinde durulmaktadır. Hipnoz, amnezi, sedasyon santral sinir sisteminde farklı reseptör, nörotransmitter ve nöronal yolaklar aracılığıyla sağlanır. 1980'lerin başında yapılan çalışmalar sonrasında, iyon kanallarına odaklanan protein temelli anestezi te-orisi, lipid temelli anestezi teorisinin yerini almıştır. Protein temelli teoriye göre, genel anestezik etkiden sorumlu iki tip reseptör mev-cuttur; nörotransmitter reseptörler ve iyon kanalları. “Background” iyon kanalları da anestezik etki için yeni tanımlanmış hedef resep-törlerdir. İki porlu (two-pore-domain) potasyum kanallarından TWIK ilişkili K+ kanalı (TREK), TWIK ilişkili araşidonik asitle aktive K+kanalı (TRAAK), TWIK ilişkili asit duyarlı K+ kanalları (TASK) tipteki kanalların volatil ajanların düşük konsantrasyonunda güçlendiği ya da bloke olduğu bildirilmiştir. İki porlu potasyum kanalları, biyolo-jik membranlarda bulunan protein kompleksleridir. İki porlu potas-yum kanalları, potasyum iyonları için özeldir ve potasyumun hücre membranından geçmesine izin verirler. İki porlu potasyum kanal-ları, nöronal uyarılma, nörotransmitter ve hormon salınımı yoluyla, membran potansiyelindeki değişikliklerden de sorumludurlar. İki porlu potasyum kanalların TASK-1 ve TREK-1 alt tipleri volatil anes-tezik ajanlarla (örneğin, izofluran, kloroform, dietil eter) uyarılır. Bu makalede santral sinir sisteminde bulunan ve genel anesteziklerin etkisinden sorumlu reseptörler ve bunların etki mekanizmaları gözden geçirilecektir.

Kaynakça

  • 1. Brown EN, Purdon PL, Van Dort CJ. General anesthesia and altered states of arousal: A systems. Annu Rev Neurosci 2011; 34: 601-28. [CrossRef ]
  • 2. Bandeiras C, Serro AP, Luzyanin K, Fernandes A, Saramago B, An-esthetics interacting with lipid rafts. Eur J Pharm Sci 2013; 48: 153-65. [CrossRef ]
  • 3. Weinrich M, Worcester DL. The actions of volatile anesthetics: a new perspective. Res Pap Acta Cryst 2018; 74: 1169-77. [CrossRef ]
  • 4. Pavel MA, Petersen EN, Lerner RA, Hansen SB. Studies on the Mechanism of General Anesthesia. BioRxiv 2018. [CrossRef ]
  • 5. Weinrich M, Worcester DL. Xenon and other volatile anesthetics change domain structure in model lipid raft membranes. J Phys Chem B 2013; 117: 16141-7. [CrossRef ]
  • 6. Gray E, Karslake J, Machta BB, Veatch SL. Liquid general anesthet-ics lower critical temperatures in plasma membrane vesicles. Bio-phys J 2013; 105: 2751-9. [CrossRef ]
  • 7. Papahadjopoulos D, Jacobson K, Poste G, Shepherd G. Effects of local anesthetics on membrane properties I changes in the fluidi-ty of phospholipid bilayers. Biochim Biophys Acta 1975; 394: 504-19. [CrossRef ]
  • 8. Lee AG. Model for action of local anaesthetics. Nature 1976; 262: 545-8. [CrossRef ]
  • 9. Vanderkooi JM, Landesberg R, Selick H, McDonald GG. Interaction of general anesthetics with phospholipid vesicles and biological membranes. Biochim. Biophys Acta 1977; 464: 1-18. [CrossRef ]
  • 10. Snyder SH. Drug and neurotransmitter receptors in the brain. Sci-ence 1984; 6: 224: 22-32. [CrossRef ]
  • 11. Keramidas A, Moorhouse AJ, Schofield PR, Barry PH. Ligand-gated ion channels: mechanisms underlying ion selectivity. Progress in Biophysics and Molecular Biology 2004; 86: 161-204. [CrossRef ]
  • 12. Gilman AG. G proteins: Transducers of Receptor-Generated Sig-nals. Annual Review of Biochemistry 1987; 56: 615-49. [CrossRef ]
  • 13. Bowery NG, Smart TG. GABA and glycine as neurotransmitters: a brief history. British Journal of Pharmacology 2006; 47: 109-19. [CrossRef ]
  • 14. Rebechii MJ, Pentyala SN. Anesthetic actions on other targets: protein kinase C and guanine nucleotide binding proteins. Br Journal of Anaesthesia 2002; 89: 62-78. [CrossRef ]
  • 15. Franks NP, Lieb WR. Molecular and cellular mechanisms of general anaesthesia. Nature 1994; 367: 607-14. [CrossRef ]
  • 16. Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE. Sites of alcohols and volatile anesthetic action on GABA (A) and glycine receptors. Nature 1997; 389; 385-9. [CrossRef ]
  • 17. Zuo Z, De Vente J, John RA. Halothane and isoflurane dose dependently inhibit the cyclic GMP increase caused by methyl D-aspartate in rat cerebellum: novel localization and quantitation by in vivo autoradiography. Neuroscience 1996; 74: 1069-75. [CrossRef ]
  • 18. Sonner JM, Antognini JF, Dutton RC, Flood P, Gray AT, Harris RA, et al. Inhaled anesthetics and immobility: mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesth Analg 2003; 97: 718-40. [CrossRef ]
  • 19. Ouyang W, Hemmings HC Jr. Depression by isoflurane of the ac-tion potential and underlying voltage-gated ion currents in iso-lated rat neurohypophysial nerve terminals. J Pharmacol Exp Ther 2005; 312: 801-8. [CrossRef ]
  • 20. Zhang Y, Laster MJ, Hara K, Harris RA, Eger EI. Glycine receptors mediate part of the immobility produced by inhaled anesthetics. Anesthesia and Analgesia 2003; 96: 97-101. [CrossRef ]
  • 21. Uwe R, Bernd A. Molecular and neuronal substrates for general anesthetics. Nature reviews of neuroscience. 2004; 4: 709-16.
  • 22. Flood P, Ramirez-Latorre J, Role L. Alpha 4 beta 2 neuronal nic-otinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha 7-type nicotinic acetylcholine receptors are unaffected. Anesthesiology 1997; 86: 859-65. [CrossRef ]
  • 23. Fagerlund MJ, Krupp J, Dabrowski MA. Propofol and AZD3043 in-hibit adult muscle and neuronal nicotinic acetylcholine receptors expressed in Xenopus Oocytes. Pharmaceuticals (Basel) 2016; 6: 9; 8. [CrossRef ]
  • 24. Flood P, Matthew K. Intravenous Anesthetics differentially modu-late ligand-gated ion channels. Anesthesiology 2000; 92: 1418-22. [CrossRef ]
  • 25. Lin LH, Chen LL, Harris RA. Enflurane inhibits NMDA, AMPA, and kainate-induced currents in Xenopus oocytes expressing mouse and human brain mRNA. FASEB J 1993; 7: 479-85. [CrossRef ]
  • 26. Maclver MB, Mikulec AA, Amagasu SM, Monroe FA. Volatile anes-thetics depress glutamate transmission via presynaptic actions. Anesthesiology 1996; 85: 823-34. [CrossRef ]
  • 27. Bruce A, Bray D. Alberts Molecular Biology of the cell. Fourth edi-tion. Mc Graw Hill, New York 2007 1224.
  • 28. Grasshoff C, Drexler B, Uwe R, Bernd A. Anaesthetic Drugs: Linking Molecular Actions to Clinical Effects. Current Pharmaceutical De-sign. 2006; 12: 3665-79. [CrossRef ]
  • 29. Kulkarni RS, Zorn LJ, Anantharam V, Bayley H, Treistman SN. Inhib-itory effects of ketamine and halothane on recombinant potas-sium channels from mammalian brain. Anesthesiology 1996; 84: 900-9. [CrossRef ]
  • 30. Harris T, Shahidullah M, Ellingson JS, Covarribias M. General anes-thetic action at an internal protein site involving the S4-S5 cyto-plasmic loop of a neuronal K(+) channel. J Biol Chem 2000; 275: 4928-36. [CrossRef ]
  • 31. Hemmings HC Jr. Sodium channels and the synaptic mechanisms of inhaled anesthetics. Br J Anaesth 2009; 103: 61-9. [CrossRef ]
  • 32. Patel AJ, Honore E, Lesage F, Fink M, Romey G, Lazdunski M. In-halational anesthetics activate two-pore domain back-ground K+ channels. Nat Neurosci 1999; 2: 416-22. [CrossRef ]
  • 33. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M. TASK, a human background K1 channel to sense external pH variations near physiological pH. EMBO J 1997; 16: 5464-71. [CrossRef ]
  • 34. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Laz-dunski M. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K1 channel. EMBO J 1996; 15: 6854-62. [CrossRef ]
  • 35. Kim D, Fujita A, Horio Y, Kurachi Y. Cloning and functional expres-sion of a novel cardiac two-pore background K1 channel (cT-BAK-1). Circ Res 1998; 82: 513-18. [CrossRef ]
  • 36. Leonoudakis D, Gray AT, Winegar BD, Kindler CH, Harada M, Taylor DM, et al. An open rectifier potassium channel with two pore do-mains in tandem cloned from rat cerebellum. J Neurosci 1998; 18: 868-77. [CrossRef ]
  • 37. Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore' E. Mecha-no- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 1999: 274: 26691-6. [CrossRef ]
  • 38. Patel AJ, Honore E, Maingret F, Lesage F, Fink M, Duprat F, et al. A mammalian two pore domain mechano-gated S-type K1 channel. EMBO J 1998; 17: 4283-90. [CrossRef ]
  • 39. Enyedi P, Czirják G. Molecular background of leak K+ currents: two-pore domain potassium channels, Physiol. Rev. 2010; 90: 559-605. [CrossRef ]
  • 40. Heurteaux C, Guy N, Laigle C, Blondeau N, Duprat F, Mazzuca M, et al. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J 2004; 23: 2684-95. [CrossRef ]
  • 41. Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP. Two-pore domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol 2004; 65: 443-452. [CrossRef ]
  • 42. Laverty D, Desai R, Uchański T, Masiulis S, Stec WJ, Malinauskas T, et al. Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer. Nature 2019; 565: 516-20. [CrossRef ]
  • 43. Michailidis IE, Helton TD, Petrou VI, Mirshahi T, Ehlers MD, Logo-thetis DE. Phosphatidylinositol-4,5-bisphosphate regulates NMDA receptor activity through alpha-actinin. J Neurosci 2007; 27: 5523-32. [CrossRef ]
  • 44. Hamouda AK, Sanghvi M, Sauls D, Machu TK, Blanton MP. Assess-ing the lipid requirements of the Torpedo californica nicotinic ace-tylcholine receptor. Biochemistry 2006, 45: 4327-37. [CrossRef ]
  • 45. Krasowski MD, Harrison NL. General anaesthetic actions on li-gand-gated ion channels. Cell Mol Life Sci 1999; 55: 1278-303. [CrossRef ]

Molecular Mechanism of General Anesthesia

Yıl 2020, Cilt 10, Sayı 3, 140 - 143, 24.12.2020
https://doi.org/10.26650/experimed.2020.824840

Öz

Despite the widespread changes induced by general anesthetic agents, their exact effect sites are not clearly defined in the central nervous system (CNS). Recent molecular studies have pointed out specific sites in CNS on which anesthetic drugs show their effects. Hypnosis, amnesia, sedation are mediated by different receptors, neurotransmitters and neuronal pathways in the CNS. Protein base theory of anesthesia, which focuses on ion channels, took the place of lipid-based theory in the 1980’s. There are two types of receptors, which are known to be responsible for the general anes-thetic action: neurotransmitter receptors and ion channels. Back-ground channels are also described as targets for anesthetic ac-tion. Enhancement and block of TWIK Related K+ channels (TREK), TWIK related arachidonic acid activated K+ channel (TRAAK), and TWIK related acid-sensitive K+ channels (TASK) channels have been reported at low concentrations of volatile anesthetic agents. Two-pore-domain potassium channels are protein complexes em-bedded in cell membranes. They selectively allow potassium ions to pass through the cellular membrane. These channels are also ca-pable of changing the membrane potential by means of neuronal excitability, neurotransmitters and hormone secretion. Of those channels, TASK-1 and TREK-1 are activated by volatile anesthetic agents. In this article, receptors responsible for anesthesia in CNS and their mechanism of action will be reviewed.

Kaynakça

  • 1. Brown EN, Purdon PL, Van Dort CJ. General anesthesia and altered states of arousal: A systems. Annu Rev Neurosci 2011; 34: 601-28. [CrossRef ]
  • 2. Bandeiras C, Serro AP, Luzyanin K, Fernandes A, Saramago B, An-esthetics interacting with lipid rafts. Eur J Pharm Sci 2013; 48: 153-65. [CrossRef ]
  • 3. Weinrich M, Worcester DL. The actions of volatile anesthetics: a new perspective. Res Pap Acta Cryst 2018; 74: 1169-77. [CrossRef ]
  • 4. Pavel MA, Petersen EN, Lerner RA, Hansen SB. Studies on the Mechanism of General Anesthesia. BioRxiv 2018. [CrossRef ]
  • 5. Weinrich M, Worcester DL. Xenon and other volatile anesthetics change domain structure in model lipid raft membranes. J Phys Chem B 2013; 117: 16141-7. [CrossRef ]
  • 6. Gray E, Karslake J, Machta BB, Veatch SL. Liquid general anesthet-ics lower critical temperatures in plasma membrane vesicles. Bio-phys J 2013; 105: 2751-9. [CrossRef ]
  • 7. Papahadjopoulos D, Jacobson K, Poste G, Shepherd G. Effects of local anesthetics on membrane properties I changes in the fluidi-ty of phospholipid bilayers. Biochim Biophys Acta 1975; 394: 504-19. [CrossRef ]
  • 8. Lee AG. Model for action of local anaesthetics. Nature 1976; 262: 545-8. [CrossRef ]
  • 9. Vanderkooi JM, Landesberg R, Selick H, McDonald GG. Interaction of general anesthetics with phospholipid vesicles and biological membranes. Biochim. Biophys Acta 1977; 464: 1-18. [CrossRef ]
  • 10. Snyder SH. Drug and neurotransmitter receptors in the brain. Sci-ence 1984; 6: 224: 22-32. [CrossRef ]
  • 11. Keramidas A, Moorhouse AJ, Schofield PR, Barry PH. Ligand-gated ion channels: mechanisms underlying ion selectivity. Progress in Biophysics and Molecular Biology 2004; 86: 161-204. [CrossRef ]
  • 12. Gilman AG. G proteins: Transducers of Receptor-Generated Sig-nals. Annual Review of Biochemistry 1987; 56: 615-49. [CrossRef ]
  • 13. Bowery NG, Smart TG. GABA and glycine as neurotransmitters: a brief history. British Journal of Pharmacology 2006; 47: 109-19. [CrossRef ]
  • 14. Rebechii MJ, Pentyala SN. Anesthetic actions on other targets: protein kinase C and guanine nucleotide binding proteins. Br Journal of Anaesthesia 2002; 89: 62-78. [CrossRef ]
  • 15. Franks NP, Lieb WR. Molecular and cellular mechanisms of general anaesthesia. Nature 1994; 367: 607-14. [CrossRef ]
  • 16. Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE. Sites of alcohols and volatile anesthetic action on GABA (A) and glycine receptors. Nature 1997; 389; 385-9. [CrossRef ]
  • 17. Zuo Z, De Vente J, John RA. Halothane and isoflurane dose dependently inhibit the cyclic GMP increase caused by methyl D-aspartate in rat cerebellum: novel localization and quantitation by in vivo autoradiography. Neuroscience 1996; 74: 1069-75. [CrossRef ]
  • 18. Sonner JM, Antognini JF, Dutton RC, Flood P, Gray AT, Harris RA, et al. Inhaled anesthetics and immobility: mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesth Analg 2003; 97: 718-40. [CrossRef ]
  • 19. Ouyang W, Hemmings HC Jr. Depression by isoflurane of the ac-tion potential and underlying voltage-gated ion currents in iso-lated rat neurohypophysial nerve terminals. J Pharmacol Exp Ther 2005; 312: 801-8. [CrossRef ]
  • 20. Zhang Y, Laster MJ, Hara K, Harris RA, Eger EI. Glycine receptors mediate part of the immobility produced by inhaled anesthetics. Anesthesia and Analgesia 2003; 96: 97-101. [CrossRef ]
  • 21. Uwe R, Bernd A. Molecular and neuronal substrates for general anesthetics. Nature reviews of neuroscience. 2004; 4: 709-16.
  • 22. Flood P, Ramirez-Latorre J, Role L. Alpha 4 beta 2 neuronal nic-otinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha 7-type nicotinic acetylcholine receptors are unaffected. Anesthesiology 1997; 86: 859-65. [CrossRef ]
  • 23. Fagerlund MJ, Krupp J, Dabrowski MA. Propofol and AZD3043 in-hibit adult muscle and neuronal nicotinic acetylcholine receptors expressed in Xenopus Oocytes. Pharmaceuticals (Basel) 2016; 6: 9; 8. [CrossRef ]
  • 24. Flood P, Matthew K. Intravenous Anesthetics differentially modu-late ligand-gated ion channels. Anesthesiology 2000; 92: 1418-22. [CrossRef ]
  • 25. Lin LH, Chen LL, Harris RA. Enflurane inhibits NMDA, AMPA, and kainate-induced currents in Xenopus oocytes expressing mouse and human brain mRNA. FASEB J 1993; 7: 479-85. [CrossRef ]
  • 26. Maclver MB, Mikulec AA, Amagasu SM, Monroe FA. Volatile anes-thetics depress glutamate transmission via presynaptic actions. Anesthesiology 1996; 85: 823-34. [CrossRef ]
  • 27. Bruce A, Bray D. Alberts Molecular Biology of the cell. Fourth edi-tion. Mc Graw Hill, New York 2007 1224.
  • 28. Grasshoff C, Drexler B, Uwe R, Bernd A. Anaesthetic Drugs: Linking Molecular Actions to Clinical Effects. Current Pharmaceutical De-sign. 2006; 12: 3665-79. [CrossRef ]
  • 29. Kulkarni RS, Zorn LJ, Anantharam V, Bayley H, Treistman SN. Inhib-itory effects of ketamine and halothane on recombinant potas-sium channels from mammalian brain. Anesthesiology 1996; 84: 900-9. [CrossRef ]
  • 30. Harris T, Shahidullah M, Ellingson JS, Covarribias M. General anes-thetic action at an internal protein site involving the S4-S5 cyto-plasmic loop of a neuronal K(+) channel. J Biol Chem 2000; 275: 4928-36. [CrossRef ]
  • 31. Hemmings HC Jr. Sodium channels and the synaptic mechanisms of inhaled anesthetics. Br J Anaesth 2009; 103: 61-9. [CrossRef ]
  • 32. Patel AJ, Honore E, Lesage F, Fink M, Romey G, Lazdunski M. In-halational anesthetics activate two-pore domain back-ground K+ channels. Nat Neurosci 1999; 2: 416-22. [CrossRef ]
  • 33. Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M. TASK, a human background K1 channel to sense external pH variations near physiological pH. EMBO J 1997; 16: 5464-71. [CrossRef ]
  • 34. Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Laz-dunski M. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K1 channel. EMBO J 1996; 15: 6854-62. [CrossRef ]
  • 35. Kim D, Fujita A, Horio Y, Kurachi Y. Cloning and functional expres-sion of a novel cardiac two-pore background K1 channel (cT-BAK-1). Circ Res 1998; 82: 513-18. [CrossRef ]
  • 36. Leonoudakis D, Gray AT, Winegar BD, Kindler CH, Harada M, Taylor DM, et al. An open rectifier potassium channel with two pore do-mains in tandem cloned from rat cerebellum. J Neurosci 1998; 18: 868-77. [CrossRef ]
  • 37. Maingret F, Patel AJ, Lesage F, Lazdunski M, Honore' E. Mecha-no- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J Biol Chem 1999: 274: 26691-6. [CrossRef ]
  • 38. Patel AJ, Honore E, Maingret F, Lesage F, Fink M, Duprat F, et al. A mammalian two pore domain mechano-gated S-type K1 channel. EMBO J 1998; 17: 4283-90. [CrossRef ]
  • 39. Enyedi P, Czirják G. Molecular background of leak K+ currents: two-pore domain potassium channels, Physiol. Rev. 2010; 90: 559-605. [CrossRef ]
  • 40. Heurteaux C, Guy N, Laigle C, Blondeau N, Duprat F, Mazzuca M, et al. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J 2004; 23: 2684-95. [CrossRef ]
  • 41. Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP. Two-pore domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol 2004; 65: 443-452. [CrossRef ]
  • 42. Laverty D, Desai R, Uchański T, Masiulis S, Stec WJ, Malinauskas T, et al. Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer. Nature 2019; 565: 516-20. [CrossRef ]
  • 43. Michailidis IE, Helton TD, Petrou VI, Mirshahi T, Ehlers MD, Logo-thetis DE. Phosphatidylinositol-4,5-bisphosphate regulates NMDA receptor activity through alpha-actinin. J Neurosci 2007; 27: 5523-32. [CrossRef ]
  • 44. Hamouda AK, Sanghvi M, Sauls D, Machu TK, Blanton MP. Assess-ing the lipid requirements of the Torpedo californica nicotinic ace-tylcholine receptor. Biochemistry 2006, 45: 4327-37. [CrossRef ]
  • 45. Krasowski MD, Harrison NL. General anaesthetic actions on li-gand-gated ion channels. Cell Mol Life Sci 1999; 55: 1278-303. [CrossRef ]

Ayrıntılar

Birincil Dil İngilizce
Konular Tıp
Bölüm Derleme
Yazarlar

Özge KÖNER Bu kişi benim
Department of Anesthesiology and Reanimation, Yeditepe University, Istanbul, Turkey
0000-0002-5618-2216
Türkiye


Sibel TEMÜR> (Sorumlu Yazar)
Department of Anesthesiology and Reanimation, Yeditepe University, Istanbul, Turkey
0000-0002-4494-2265
Türkiye


Turgay İŞBİR>
Department of Molecular Medicine, Yeditepe University, Istanbul, Turkey
0000-0002-7350-6032
Türkiye

Destekleyen Kurum yoktur
Yayımlanma Tarihi 24 Aralık 2020
Başvuru Tarihi 12 Kasım 2020
Kabul Tarihi 1 Aralık 2020
Yayınlandığı Sayı Yıl 2020, Cilt 10, Sayı 3

Kaynak Göster

Bibtex @derleme { experimed824840, journal = {Experimed}, eissn = {2667-5846}, address = {}, publisher = {İstanbul Üniversitesi}, year = {2020}, volume = {10}, number = {3}, pages = {140 - 143}, doi = {10.26650/experimed.2020.824840}, title = {Molecular Mechanism of General Anesthesia}, key = {cite}, author = {Köner, Özge and Temür, Sibel and İşbir, Turgay} }
APA Köner, Ö. , Temür, S. & İşbir, T. (2020). Molecular Mechanism of General Anesthesia . Experimed , 10 (3) , 140-143 . DOI: 10.26650/experimed.2020.824840
MLA Köner, Ö. , Temür, S. , İşbir, T. "Molecular Mechanism of General Anesthesia" . Experimed 10 (2020 ): 140-143 <https://dergipark.org.tr/tr/pub/experimed/issue/58591/824840>
Chicago Köner, Ö. , Temür, S. , İşbir, T. "Molecular Mechanism of General Anesthesia". Experimed 10 (2020 ): 140-143
RIS TY - JOUR T1 - Genel Anesteziklerin Moleküler Mekanizması AU - ÖzgeKöner, SibelTemür, Turgayİşbir Y1 - 2020 PY - 2020 N1 - doi: 10.26650/experimed.2020.824840 DO - 10.26650/experimed.2020.824840 T2 - Experimed JF - Journal JO - JOR SP - 140 EP - 143 VL - 10 IS - 3 SN - -2667-5846 M3 - doi: 10.26650/experimed.2020.824840 UR - https://doi.org/10.26650/experimed.2020.824840 Y2 - 2020 ER -
EndNote %0 Experimed Molecular Mechanism of General Anesthesia %A Özge Köner , Sibel Temür , Turgay İşbir %T Molecular Mechanism of General Anesthesia %D 2020 %J Experimed %P -2667-5846 %V 10 %N 3 %R doi: 10.26650/experimed.2020.824840 %U 10.26650/experimed.2020.824840
ISNAD Köner, Özge , Temür, Sibel , İşbir, Turgay . "Molecular Mechanism of General Anesthesia". Experimed 10 / 3 (Aralık 2020): 140-143 . https://doi.org/10.26650/experimed.2020.824840
AMA Köner Ö. , Temür S. , İşbir T. Molecular Mechanism of General Anesthesia. Experimed. 2020; 10(3): 140-143.
Vancouver Köner Ö. , Temür S. , İşbir T. Molecular Mechanism of General Anesthesia. Experimed. 2020; 10(3): 140-143.
IEEE Ö. Köner , S. Temür ve T. İşbir , "Molecular Mechanism of General Anesthesia", Experimed, c. 10, sayı. 3, ss. 140-143, Ara. 2020, doi:10.26650/experimed.2020.824840