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2002 | 49 | 4 |
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Transmembrane segment M2 of glycine receptor as a model system for the pore-forming structure of ion channels

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The glycine receptor belongs to the ligand-gated ion channel superfamily. It is a chlo­ride conducting channel composed of four transmembrane domains. It was previously shown that the second transmembrane domain (M2) of the glycine receptor forms an ion conduction pathway throught lipid bilayers. The amino-acid sequence of the transmembrane segment M2 of the glycine receptor has a high homology to all recep­tors of the ligand-gated ion channel superfamily. In our report, we have used a syn­thetic M2 peptide. It was incorporated into a planar membrane of known lipid compo­sition and currents induced by M2 were measured by the Black Lipid Membrane tech­nique. When the planar lipid bilayer was composed of 75% phosphatidylethanolamine and 25% phosphatidylserine, the reversal potential measured in a 150/600 mM KCl (cis/trans) gradient was -19 mV suggesting that the examined pore was preferential to anions, Pk/Pci = 0.25. In contrast, when 75% phosphatidylserine and 25% phosphatidylethanolamine was used, the reversal potential was +20 mV and the pore was preferential to cations, Pk/Pci = 4.36. Single-channel currents were recorded with two predominant amplitudes corresponding to the main-conductance and sub-conductance states. Both conductance states (about 12 pS and 30 pS) were mea­sured in a symmetric solution of 50 mM KCl. The observed single-channel properties suggest that the selectivity and conductance of the pore formed by the M2 peptide of the glycine receptor depend on the lipid composition of the planar bilayer.
Opis fizyczny
  • Agricultural University, Rakowiecka 26-30, 02-528 Warsaw, Poland
  • Adcock C, Smith GR, Sansom MS. (1998) Electrostatics and the ion selectivity of ligand-gated channels. Biophys J.; 75: 1211-22.
  • Aguilella VM, Bezrukov SM. (2001) Alamethicin channel conductance modified by lipid charge. Eur Biophys J. ; 30: 233-41.
  • Anzai K, Takano C, Tanaka K, Kirino Y. (1994) Asymmetrical lipid charge changes the subconducting state of the potassium channel from sarcoplasmic reticulum. Biochem Biophys Res Commun.; 199: 1081-7.
  • Bormann J, Feigenspan A. (1995) GABAC receptors. Trends Neurosci.; 18: 515-9.
  • Bormann J, Hamill OP, Sakmann B. (1987) Mechanism of anion permeation through channels gated by glycine and gamma-aminobutyric acid in mouse cultured spinal neurones. J Physiol.; 385: 243-86.
  • Cascio M, Shenkel S, Grodzicki RL, Sigworyh FJ, Fox RO. (2001) Functional reconstitution and characterization of recombinant human alpha1-glycine receptors. J Biol Chem.; 276: 20981-8.
  • De Godoy CMG, Cukierman S. (2001) Modulation of proton transfer in the water wire of dioxolane-linked gramicidin channels by lipid membranes. Biophys J.; 81: 1430-8.
  • Fan Z, Makielski JC. (1997) Anionic phospholipids activate ATP-sensitive potassium channels. J Biol Chem.; 272: 5388-95.
  • Hille B. (2001) Selective permeability: independence. In Ion channels ofexcitable membranes. pp 441-70. Sinauer Associates Inc., Sunderland, U S A.
  • Karlin A. (1993) Structure of nicotinic acetylcholine receptors. Curr Opin Neurobiol.; 3: 299-309.
  • Keramidas A, Moorhouse AJ, Pierce KD, Schofield PR, Barry PH. (2002) Cation-selective mutations in the M2 domain of the inhibitory glycine receptor channel reveal determinants of ion-charge selectivity. J Gen Physiol.; 119: 393-410.
  • Kuhse J, Betz H, Kirsch J. (1995) The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex. Curr Opin Neurobiol.; 5: 318-23.
  • Langosch D. (1995) Inhibitory glycine receptors. In Receptors and channels. Ligand- and voltage-gated ion channels. pp 291-305. CRC Press, Boca Raton.
  • Langosch D, Hartung K, Grell E, Bamberg E, Betz H. (1991) Ion channel formation by synthetic transmembrane segments of the inhibitory glycine receptor — a model study. Biochim Biophys Acta.; 1063: 36-44.
  • Leite JF, Cascio M. (2001) Structure of ligand-gated ion channels: critical assessment of biochemical data supports novel topology. Mol Cell Neurosci.; 17: 777-92.
  • Nalecz MJ, Zborowski J, Famulski KS, Wojtczak L. (1980) Effect of phospholipid composition on the surface potential of liposomes and the activity of enzymes incorporated. Eur J Biochem.; 112: 75-80.
  • Nicholls JG, Martin AR, Wallace BG, Fuchs PA. (2001) Structure of ion channels. In From neuron to brain. pp 39-59. Sinauer Associates Inc., Massachusetts, U S A.
  • Reddy GL, Iwamoto T, Tomich JM, Montai M. (1993) Synthetic peptides and four-helix bundle proteins as model system for the pore-forming structure of channel proteins. J Biol Chem.; 268: 14608-15.
  • Reeves DC, Lummis SC. (2002) The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand- gated ion channel. Mol Membr Biol.; 19: 11-26.
  • Rostovtseva TK, Aguilella VM, Vodyanoy I, Bezrukov SM, Parsegian VA. (1998) Membrane surface-charge titration probed by gramicidin A channel conductance. Biophys J.; 75: 1783-92.
  • Sieghart W. (1995) Structure and pharmacology of gamma-aminobutyric acid A receptor subtypes. Pharmacol Rev.; 47: 181-234.
  • Sieghart W, Sperk G. (2002) Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr Top Med Chem.; 2: 795-816.
  • Sprong H, van der Sluijs P, van Meer G. (2001) How proteins move lipids and lipids move proteins. Nat Rev Mol Cell Biol.; 2: 504-13.
  • Twyman RE, Macdonald RL. (1991) Kinetic properties of the glycine receptor main- and sub-conductance states of mouse spinal cord neurons in culture. J Physiol.; 435: 303-31.
  • Tyndale RF, Olsen RW, Tobin AJ. (1995) GABAa receptors. In Receptors and channels. Ligand- and voltage-gated ion channels. pp 265-90. CRC Press, Boca Raton.
  • Wallace DP, Tomich JM, Eppler JW, Iwamoto T, Grantham JJ, Sullivan LP. (2000) A synthetic channel-forming peptide includes Cl- secretion: modulation by Ca2+-dependent K+ channels. Biochim Biophys Acta.; 1464: 69-82.
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