Xenon blocks AMPA and NMDA receptor channels by different mechanisms

• Autorzy: Weigt H.U. , Fohr K. J. , Georgieff M. , Georgieff E. M. , Senftleben U. , Adolph O.
• Języki publikacji: EN

Abstrakty

EN

The noble gas xenon (Xe) inhibits not only NMDA receptors (NMDARs), but also the two other subtypes of glutamate receptor i.e. AMPA (AMPARs) and kainate receptors. Preliminary studies on AMPARs suggest that Xe sensitivity might be coupled to receptor desensitization. In order to find out if this hypothesis can be applied to all glutamate receptors, we analyzed additional “non-desensitizing” AMPARs mutants and compared these with homologous mutants of NMDARs. Membrane currents of Neuro2A or SH-SY5Y cells transfected with cDNA encoding AMPA- or NMDA receptors were investigated by whole cell recordings under voltage clamp conditions. Agonists (glutamate, kainate, NMDA) were applied to the cells by means of a rapid perfusion system. Xenon was preincubated for 20 s before testing it in combination with the particular agonist. Xe (3.5 mM) reduced peak and plateau currents of AMPA wild-type receptors [GluR1(i); GluR2(i,Q)], activated for 5 s with 3 mM glutamate, by 45 and 55%, respectively. With mutant AMPARs showing greatly diminished or abolished desensitization i.e. GluR1(i)_L497Y, GluR1(i)_A636T(Lc), GluR2(i,Q)_R649E and GluR2(i,Q)_A643T(Lc), the reduction by Xe was significantly smaller and varied by between 4 and 20%. In contrast, no difference in the blocking capacity of Xe was observed comparing wild-type NR1-1a/NR2A receptors with receptors having point mutations within NR2A that substantially slowed (NR2A_A651T(Lc)) or accelerated (NR2A_M823W) receptor desensitization. Thus, our data indicate that in AMPARs channel blockade by Xe is related to desensitization, whereas in NMDARs no evidence for such a relation was found. Thus, Xe seems to exert its inhibiting effect on various ionotropic glutamate receptors by different molecular mechanisms.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 4
• Opis fizyczny: p.429–440,fig.,ref.

Twórcy

autor

Weigt H.U.

• Department of Anaesthesiology, SLK-Kliniken Heilbronn, Bad Friedrichshall, Germany

autor

Fohr K. J.

• Department of Anaesthesiology, Ulm University, Ulm, Germany

autor

Georgieff M.

• Department of Anaesthesiology, Ulm University, Ulm, Germany

autor

Georgieff E. M.

• Department of Anaesthesiology, Ulm University, Ulm, Germany

autor

Senftleben U.

• Department of Anaesthesiology, Ulm University, Ulm, Germany

autor

Adolph O.

• Department of Anaesthesiology, Ulm University, Ulm, Germany

Bibliografia

• Cullen C, Gross C (1951) The anesthetic properties of xenon in animals and human beings, with additional observa­tions on krypton. Science 113: 580-582.
• deSousa S, Dickinson R, Lieb W, Franks N (2000) Contrasting Synaptic Actions of the Inhalational General Anesthetics Isoflurane and Xenon. Anesthesiology 92: 1055-1066.
• Dinse A, Fohr KJ, Georgieff M, Beyer C, Bulling A, Weigt HU (2005) Xenon reduces glutamate-, AMPA- and kain- ate-induced membrane currents in cortical neurons. Br J Anaesth 94: 479-485.
• Erreger K, Traynelis S (2005) Allosteric interaction between zinc and glutamate binding domains on NR2A causes desen- sitization of NMDA receptors. J Physiol 569: 381-393.
• Franks NP, Dickinson R, deSousa SL, Hall AC, Lieb WR (1998) How does xenon produce anesthesia? Nature 396: 324.
• Furukawa H, Singh SK, Mancusso R (2005) Subunit arrangement and function in NMDA receptors. Nature 438: 185-192.
• Gruss MG, Bushell TJ, Bright DP, Lieb AR, Mathie A, Franks NP (2004) Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol 65: 443-452.
• Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolu­tion current recording from cells and cell-free membrane patches. Pflugers Arch 391: 85-100.
• Hapfelmeier G, Zieglgansberger W, Haseneder R, Schneck H, Kochs E (2000) Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABAa receptors. Anesth Analg 91: 1542-1549.
• Haseneder R, Kratzer S, Kochs E, Eckle VS, Ziegelgansberger W, Rammes G (2008) Xenon reduces N-methyl-D-aspartate and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated synaptic transmission in the amy­gdala. Anesthesiology 109: 998-1006.
• Jackson MF, Joo DT, Al-Mahrouki AA (2003) Desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropion- ic acid (AMPA) receptors facilitates use-dependent inhi­bition by pentobarbital. Mol Pharmacol 64: 395-406.
• Khoda K, Wang Y, Yuzaki M (2000) Mutation of a gluta­mate receptor motif reveals its role in gating and delta2 receptor channel properties. Nat Neurosci 3: 315-322.
• Klein RM, Howe JR (2004) Effects of the lurcher mutation on GluRl desensitization and activation kinetics. J Neurosci 24: 4941-4951.
• Koike M, Tsukada S, Tsuzuki K (2000) Regulation of kinet­ic properties of GluR2 AMPA receptor channels by alter­native splicing. J Neurosci 20: 2166-2174.
• Krupp JJ, Vissel B, Heinemann SF (1996) Calcium- dependent inactivation of recombinant N-methyl-D- aspartate receptors is NR2 subunit specific. Mol Pharmacol 50: 1680-1688.
• Krupp JJ, Vissel B, Heinemann SF (1998) N-terminal domains in the NR2 subunit control desensitization of NMDA receptors. Neuron 20: 317-327.
• Kutsuwada T, Kashiwabuchi N, Mori H, Sakimura K, Kushiya E, Araki K, Meguro H, Masaki H, Kumanishi T, Arakawa M, Mishina M (1992) Molecular diversity of the NMDA receptor channel. Nature 358: 36-41.
• Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg P (1992) Heterooligomeric NMDA receptors: molecular und func­tional distinction of subtypes. Science 256: 1217-1221.
• Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S (1991) Molecular cloning und characteriza­tion of the rat NMDA receptor. Nature 354: 31-37.
• Nagele P, Metz LB, Crowder M (2005) Xenon acts by inhi­bition of non-N-methyl-D-aspartate receptor-
• mediated glutamatergic neurotransmission in Caenorhabditis elegans. Anesthesiology 103: 508-513.
• Partin KM, Patneau DK, Mayer ML (1994) Cyclothiazide differentially modulates desensitization of alpha-amino-3 -hydroxy-5-methyl-4-isoxazolepropionic acid receptor splice variants. Mol Pharmacol 46: 129-138.
• Patneau DK, Vyklicky Jr. L, Mayer ML (1993) Hippocampal neurons exhibit cyclothiazide-sensitive radpidly desen­sitizing responses to kainate. J Neurosci 13: 3496­3509.
• Plested AJ, Wildman SS, Lieb WR, Franks NP (2004) Determinants of the sensitivity of AMPA receptors to xenon. Anesthesiology 100: 347-358.
• Rachline J, Perin-Dureau F, Le Goff A (2005) The micromo­lar zinc-binding domain on the NMDA receptor subunit NR2B. J Neurosci 25: 308-317.
• Ren H, Honse Y, Karp BJ (2003) A site in the fourth mem­brane-associated domain of the N-methyl-D-aspartate receptor regulates desensitization and ion channel gating. J Biol Chem 278: 276-283.
• Robert A, Irizarry SN, Hughes TE, Howe JR (2001) Subunit Interactions and AMPA receptor desensitization. J Neurosci 21: 5574-5586.
• Rubin CM, Kimura RH, Schmid CW (2002) Selective stimulation of translational expression by Alu RNA. Nucleic Acids Res 30: 3253-3261.
• Sather W, Johnson JW, Henderson G, Ascher P (1990) Glycine-insensitive desensitization of NMDA responses in cultured mouse embryonic neurons. Neuron 4: 725-731.
• Schwarz MK, Pawlak V, Osten P, Mack V, Seeburg PH, Köhr G (2001) Dominance of the lurcher mutation in heteromeric kainate and AMPA receptor channels. Eur J Neurosci 14: 861-868.
• Sobolevsky AI, Rooney L, Wollmuth LP (2002) Staggering of subunits in NMDAR channels. Biophys J 83: 3304-3314.
• Sommer B, Kainänen K, Verdoorn TA, Wisden W, Burnashev N, Huber A, Köhler M, Takagi T, Sakmann B, Seeburg PH (1990) Flip and flop: A cell-specific functional swith in glutamate-operated channels of the CNS. Science 249: 1580-1585.
• Stern-Bach Y, Russo S, Neuman M, Rosenmund C (1998) A point mutation in the glutamate binding site blocks desen- sitizition of AMPA receptors. Neuron 21: 907-918.
• Sun Y, Olson R, Horning M (2002) Mechanism of glutamate receptor desensitization. Nature 417: 245-253.
• Weigt HU, Adolph O, Georgieff M, Georgieff EM, Föhr KJ (2008) Evidence that xenon does not produce open chan­nel blockade of the NMDA receptor. J Neurophysiol 99: 1983-1987.
• Yelshansky MV, Sobolevsky AI, Jatzke C (2004) Block of AMPA receptor desensitization by a point mutation out­side the ligand-binding domain. J Neurosci 24: 4728­3476.
• Yuan H, Erreger K, Dravid SM, Trynelis ST (2005) Conserved structural and functional control of 'N-methyl- D-asparatate receptor gating by transmembrane domain M3. J Biol Chem 280: 29708-29716.
• Zheng F, Erreger K, Low CM (2001) Allosteric interaction between the amino terminal domain and the ligand bind­ing domain of NR2A. Nat Neurosci 4: 894-901.

Uwagi

PL

Rekord w opracowaniu