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Effects of membrane lipids on ion channel structure and function

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Abstract

Biologic membranes are not simply inert physical barriers, but complex and dynamic environments that affect membrane protein structure and function. Residing within these environments, ion channels control the flux of ions across the membrane through conformational changes that allow transient ion flux through a central pore. These conformational changes may be modulated by changes in transmembrane electrochemical potential, the binding of small ligands or other proteins, or changes in the local lipid environment. Ion channels play fundamental roles in cellular function and, in higher eukaryotes, are the primary means of intercellular signaling, especially between excitable cells such as neurons. The focus of this review is to examine how the composition of the bilayer affects ion channel structure and function. This is an important consideration because the bilayer composition varies greatly in different cell types and in different organellar membranes. Even within a membrane, the lipid composition differs between the inner and outer leaflets, and the composition within a given leaflet is both heterogeneous and highly dynamic. Differential packing of lipids (and proteins) leads to the formation of microdomains, and lateral diffusion of these microdomains or “lipid rafts” serve as mobile platforms for the clustering and organization of bilayer constituents including ion channels. The structure and function of these channels are sensitive to specific chemical interactions with neighboring components of the membrane and also to the biophysical properties of their membrane microenvironment (e.g., fluidity, lateral pressure profile, and bilayer thickness). As specific examples, we have focused on the K+ ion channels and the ligand-gated nicotinicoid receptors, two classes of ion channels that have been well-characterized structurally and functionally. The responsiveness of these ion channels to changes in the lipid environment illustrate how ion channels, and more generally, any membrane protein, may be regulated via cellular control of membrane composition.

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References

  1. Dowhan, W. (1997) Molecular basis for membrane phospholipid diversity: Why are there so many lipids. Annu. Rev. Biochem. 66, 199–232.

    PubMed  CAS  Google Scholar 

  2. White, S. H. and Wimley, W. C. (1999) Membrane protein folding and stability: Physical principles. Annu. Rev. Biophys. Biomol. Struct. 28, 319–365.

    PubMed  CAS  Google Scholar 

  3. Popot, J. L. and Engelman, D. M. (2000) Helical membrane protein folding, stability, and evolution. Annu. Rev. Biochem. 69, 881–922.

    PubMed  CAS  Google Scholar 

  4. Grigorieff, N., Ceska, T. A., Downing, K. H., Baldwin, J. M., and Henderson, R. (1996) Electron-crystallographic refinement of the structure of bacteriorhodopsin. J. Mol. Biol. 259, 393–421.

    PubMed  CAS  Google Scholar 

  5. Joshi, M. K., Dracheva, S., Mukhopadhyay, A. K., Bose, S., and Hendler, R. W. (1998) Importance of specific native lipids in controlling the photocycle of bacteriorhodopsin. Biochemistry 37, 14463–14470.

    PubMed  CAS  Google Scholar 

  6. le Maire, M., Champeil, P., and Moller, J. V. (2000) Interaction of membrane proteins and lipids with solubilizing detergents. Biochim. Biophys. Acta 1508, 86–111.

    PubMed  Google Scholar 

  7. Ridder, A. N., Morein, S., Stam, J. G., Kuhn, A., de Kruijff, B., and Killian, J. A. (2000) Analysis of the role of interfacial tryptophan residues in controlling the topology of membrane proteins. Biochemistry 39, 6521–6528.

    PubMed  CAS  Google Scholar 

  8. Yau, W. M., Wimley, W. C., Gawrisch, K., and White, S. H. (1998) The preference of tryptophan for membrane interfaces. Biochemistry 37, 14713–14718.

    PubMed  CAS  Google Scholar 

  9. Wimley, W. C., and White, S. H. (1996) Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat. Struct. Biol. 3, 842–848.

    PubMed  CAS  Google Scholar 

  10. Schiffer, M., Chang, C. H., and Stevens, F. J. (1992) The functions of tryptophan residues in membrane proteins. Protein Eng. 5, 213–214.

    PubMed  CAS  Google Scholar 

  11. Rees, D. C., DeAntonio, L., and Eisenberg, D. (1989) Hydrophobic organization of membrane proteins. Science 245, 510–513.

    PubMed  CAS  Google Scholar 

  12. Ubarretxena-Belandia, I., and Engelman, D. M. (2001) Helical membrane proteins: diversity of functions in the context of simple architecture. Curr. Opin. Struct. Biol. 11, 370–376.

    PubMed  CAS  Google Scholar 

  13. Eilers, M., Patel, A. B., Liu, W., and Smith, S. O. (2002) Comparison of helix interactions in membrane and soluble alpha-bundle proteins. Biophys. J. 82, 2720–2736.

    PubMed  CAS  Google Scholar 

  14. Choma, C., Gratkowski, H., Lear, J. D., and DeGrado, W. F. (2000) Asparagine-mediated self-association of a model transmembrane helix. Nat. Struct. Biol. 7, 161–166.

    PubMed  CAS  Google Scholar 

  15. Zhou, F. X., Cocco, M. J., Russ, W. P., Brunger, A. T., and Engelman, D. M. (2000) Interhelical hydrogen bonding drives strong interactions in membrane proteins. Nat. Struct. Biol. 7, 154–160.

    PubMed  CAS  Google Scholar 

  16. Doyle, D. A., Morais Cabral, J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., and MacKinnon, R. (1998) The structure of the potassium channel: Molecular basis of K+ conduction and selectivity. Science 280, 69–77.

    PubMed  CAS  Google Scholar 

  17. Zhou, Y., Morais-Cabral, J. H., Kaufman, A., and MacKinnon, R. (2001) Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 Å resolution. Nature 414, 43–48.

    PubMed  CAS  Google Scholar 

  18. Fu, D., Libson, A., Miercke, L. J., Weitzman, C., Nollert, P., Krucinski, J., and Stroud, R. M. (2000) Structure of a glycerol-conducting channel and the basis for its selectivity. Science 290, 481–486.

    PubMed  CAS  Google Scholar 

  19. Dutzler, R., Campbell, E. B., Cadene, M., Chait, B. T., and MacKinnon, R. (2002) X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 415, 287–294.

    PubMed  CAS  Google Scholar 

  20. Lodish, H. F. (1988) Multi-spanning membrane proteins: How accurate are the models? Trends Biochem. Sci. 13, 332–334.

    PubMed  CAS  Google Scholar 

  21. Hamasaki, N., Abe, Y., and Tanner, M. J. (2002) Flexible regions within the membrane-embedded portions of polytopic membrane proteins. Biochemistry 41, 3852–3854.

    PubMed  CAS  Google Scholar 

  22. Pebay-Peyroula, E., and Rosenbusch, J. P. (2001) High-resolution structures and dynamics of membrane protein—lipid complexes: A critique. Curr. Opin. Struct. Biol. 11, 427–432.

    PubMed  CAS  Google Scholar 

  23. Fyfe, P. K., McAuley, K. E., Roszak, A. W., Isaacs, N. W., Cogdell, R. J., and Jones, M. R. (2001) Probing the interface between membrane proteins and membrane lipids by X-ray crystallography. Trends Biochem. Sci. 26, 106–112.

    PubMed  CAS  Google Scholar 

  24. Marsh, D. and Horvath, L. I. (1998) Structure, dynamics and composition of the lipid-protein interface. Perspectives from spin-labelling. Biochim. Biophys. Acta 1376, 267–296.

    PubMed  CAS  Google Scholar 

  25. Melkonian, K. A., Ostermeyer, A. G., Chen, J. Z., Roth, M. G., and Brown, D. A. (1999) Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J. Biol. Chem. 274, 3910–3917.

    PubMed  CAS  Google Scholar 

  26. Anderson, R. G. and Jacobson, K. A. (2002) role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296, 1821–1825.

    PubMed  CAS  Google Scholar 

  27. Bogdanov, M. and Dowhan, W. (1999) Lipid-assisted protein folding. J. Biol. Chem. 274, 36827–36830.

    PubMed  CAS  Google Scholar 

  28. Bogdanov, M. and Dowhan, W. (1998) Phospholipid-assisted protein folding: Phosphatidylethanolamine is required at a late step of the conformational maturation of the polytopic membrane protein lactose permease. Embo J. 17, 5255–5264.

    PubMed  CAS  Google Scholar 

  29. Freudl, R., Schwarz, H., Stierhof, Y. D., Gamon, K., Hindennach, I., and Henning, U. (1986) An outer membrane protein (OmpA) of Escherichia coli K-12 undergoes a conformational change during export. J. Biol. Chem. 261, 11355–11361.

    PubMed  CAS  Google Scholar 

  30. de Cock, H., van Blokland, S., and Tommassen, J. (1996) In vitro insertion and assembly of outer membrane protein PhoE of Escherichia coli K-12 into the outer membrane. Role of Triton X-100. J. Biol. Chem. 271, 12885–12890.

    PubMed  Google Scholar 

  31. Holzenburg, A., Engel, A., Kessler, R., Manz, H. J., Lustig, A., and Aebi, U. (1989) Rapid isolation of OmpF porin-LPS complexes suitable for structure-function studies. Biochemistry 28, 4187–4193.

    PubMed  CAS  Google Scholar 

  32. Eisele, J. L. and Rosenbusch, J. P. (1990) In vitro folding and oligomerization of a membrane protein. Transition of bacterial porin from random coil to native conformation. J. Biol. Chem. 265, 10217–10220.

    PubMed  CAS  Google Scholar 

  33. Ferguson, A. D., Welte, W., Hofmann, E., Lindner, B., Holst, O., Coulton, J. W., and Diederichs, K. (2000) A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins. Structure Fold Des 8, 585–592.

    PubMed  CAS  Google Scholar 

  34. Hwang, P. M. and Vogel, H. J. (1998) Structure-function relationships of antimicrobial peptides. Biochem. Cell Biol. 76, 235–246.

    PubMed  CAS  Google Scholar 

  35. Johnson, J. E. and Cornell, R. B. (1999) Amphitropic proteins: regulation by reversible membrane interactions (review). Mol. Membr. Biol. 16, 217–235.

    PubMed  CAS  Google Scholar 

  36. Fivaz, M., Abrami, L., and van der Goot, F. G. (1999) Landing on lipid rafts. Trends Cell Biol. 9, 212–213.

    PubMed  CAS  Google Scholar 

  37. Schwarze, S. R. and Dowdy, S. F. (2000) In vivo protein transduction: intracellular delivery of biologically active proteins, compounds and DNA. Trends Pharmacol. Sci. 21, 45–48.

    PubMed  CAS  Google Scholar 

  38. Naslavsky, N., Shmeeda, H., Friedlander, G., Yanai, A., Futerman, A. H., Barenholz, Y., and Taraboulos, A. (1999) Sphingolipid depletion increases formation of the scrapie prion protein in neuroblastoma cells infected with prions. J. Biol. Chem. 274, 20763–20771.

    PubMed  CAS  Google Scholar 

  39. Kurzchalia, T. V. and Parton, R. G. (1999) Membrane microdomains and caveolae. Curr. Opin. Cell Biol. 11, 424–431.

    PubMed  CAS  Google Scholar 

  40. Mahfoud, R., Garmy, N., Maresca, M., Yahi, N., Puigserver, A., and Fantini, J. (2002) Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins. J. Biol. Chem. 277, 11292–11296.

    PubMed  CAS  Google Scholar 

  41. Jo, E., McLaurin, J., Yip, C. M., St George-Hyslop, P., and Fraser, P. E. (2000) α-Synuclein membrane interactions and lipid specificity. J. Biol. Chem. 275, 34328–34334.

    PubMed  CAS  Google Scholar 

  42. Lehtonen, J. Y. and Kinnunen, P. K. (1997) Evidence for phospholipid microdomain formation in liquid crystalline liposomes reconstituted with Escherichia coli lactose permease. Biophys. J. 72, 1247–1257.

    PubMed  CAS  Google Scholar 

  43. Polozova, A. and Litman, B. J. (2000) Cholesterol dependent recruitment of di22:6-PC by a G protein-coupled receptor into lateral domains. Biophys. J. 79, 2632–2643.

    PubMed  CAS  Google Scholar 

  44. Epand, R. M., Maekawa, S., Yip, C. M., and Epand, R. F. (2001) Protein-induced formation of cholesterol-rich domains. Biochemistry 40, 10514–10521

    PubMed  CAS  Google Scholar 

  45. daCosta, C. J., Ogrel, A. A., McCardy, E. A., Blanton, M. P., and Baenziger, J. E. (2002) Lipid-protein interactions at the nicotinic acetylcholine receptor. A functional coupling between nicotinic receptors and phosphatidic acid- containing lipid bilayers. J. Biol. Chem. 277, 201–208.

    PubMed  CAS  Google Scholar 

  46. Radhakrishnan, A. and McConnell, H. M. (2000) Chemical activity of cholesterol in membranes. Biochemistry 39, 8119–8124.

    PubMed  CAS  Google Scholar 

  47. Miao, L., Nielsen, M., Thewalt, J., Ipsen, J. H., Bloom, M., Zuckermann, M. J., and Mouritsen, O. G. (2002) From lanosterol to cholesterol: structural evolution and differential effects on lipid bilayers. Biophys. J. 82, 1429–1444.

    PubMed  CAS  Google Scholar 

  48. Barenholz, Y. (2002) Cholesterol and other membrane active sterols: from membrane evolution to “rafts”. Prog. Lipid Res. 41, 1–5.

    PubMed  CAS  Google Scholar 

  49. Gimpl, G., Burger, K., and Fahrenholz, F. (1997) Cholesterol as modulator of receptor function. Biochemistry 36, 10959–10974.

    PubMed  CAS  Google Scholar 

  50. Ding, J., Starling, A. P., East, J. M., and Lee, A. G. (1994) Binding sites for cholesterol on Ca2+-ATPase studies by using a cholesterol-containing phospholipid. Biochemistry 33, 4974–4979.

    PubMed  CAS  Google Scholar 

  51. Niu, S. L., Mitchell, D. C., and Litman, B. J. (2002) Manipulation of cholesterol levels in rod disk membranes by methyl-β-cyclodextrin. Effects on receptor activation. J. Biol. Chem. 277, 20139–20145.

    PubMed  CAS  Google Scholar 

  52. Booth, P. J., Templer, R. H., Meijberg, W., Allen, S. J., Curran, A. R., and Lorch, M. (2001) In vitro studies of membrane protein folding. Crit. Rev. Biochem. Mol. Biol. 36, 501–603.

    PubMed  CAS  Google Scholar 

  53. Cantor, R. S. (1999) Lipid composition and the lateral pressure profile in bilayers. Biophys. J. 76, 2625–2639.

    PubMed  CAS  Google Scholar 

  54. Cantor, R. S. (2002) Size distribution of barrelstave aggregates of membrane peptides: Influence of the bilayer lateral pressure profile. Biophys. J. 82, 2520–2525.

    PubMed  CAS  Google Scholar 

  55. Epand, R. M. (1998) Lipid polymorphism and protein-lipid interactions. Biochim. Biophys. Acta 1376, 353–368.

    PubMed  CAS  Google Scholar 

  56. Nielsen, C., Goulian, M., and Andersen, O. S. (1998) Energetics of inclusion-induced bilayer deformations. Biophys. J. 74, 1966–1983.

    PubMed  CAS  Google Scholar 

  57. Curran, A. R., Templer, R. H., and Booth, P. J. (1999) Modulation of folding and assembly of the membrane protein bacteriorhodopsin by intermolecular forces within the lipid bilayer. Biochemistry 38, 9328–9336.

    PubMed  CAS  Google Scholar 

  58. Spencer, R. H., Chang, G., and Rees, D. C. (1999) ‘Feeling the pressure’: Structural insights into a gated mechanosensitive channel. Curr. Opin. Struct. Biol. 9, 448–454.

    PubMed  CAS  Google Scholar 

  59. Hamill, O. P., and Martinac, B. (2001) Molecular basis of mechanotransduction in living cells. Physiol. Rev. 81, 685–740.

    PubMed  CAS  Google Scholar 

  60. Patel, A. J., Lazdunski, M., and Honore, E. (2001) Lipid and mechano-gated 2P domain K+ channels. Curr. Opin. Cell Biol. 13, 422–428.

    PubMed  CAS  Google Scholar 

  61. Perozo, E., Cortes, D. M., Sompornpisut, P., Kloda, A., and Martinac, B. (2002) Open channel structure of MscL and the gating mechanism of mechanosensitive channels. Nature 418, 942–948.

    PubMed  CAS  Google Scholar 

  62. Baenziger, J. E., Darsaut, T. E., and Morris, M. L. (1999) Internal dynamics of the nicotinic acetylcholine receptor in reconstituted membranes. Biochemistry 38, 4905–4911.

    PubMed  CAS  Google Scholar 

  63. Ren, J., Lew, S., Wang, J., and London, E. (1999) Control of the transmembrane orientation and interhelical interactions within membranes by hydrophobic helix length. Biochemistry 38, 5905–5912.

    PubMed  CAS  Google Scholar 

  64. Ren, J., Lew, S., Wang, Z., and London, E. (1997) Transmembrane orientation of hydrophobic alpha-helices is regulated both by the relationship of helix length to bilayer thickness and by the cholesterol concentration. Biochemistry 36, 10213–10220.

    PubMed  CAS  Google Scholar 

  65. Mall, S., Broadbridge, R., Sharma, R. P., Lee, A. G., and East, J. M. (2000) Effects of aromatic residues at the ends of transmembrane α-helices on helix interactions with lipid bilayers. Biochemistry 39, 2071–2078.

    PubMed  CAS  Google Scholar 

  66. Lewis, B. A., and Engelman, D. M. (1983) Lipid bilayer thickness varies linearly with acyl chain length in fluid phosphatidylcholine vesicles. J. Mol. Biol. 166, 211–217.

    PubMed  CAS  Google Scholar 

  67. Sankaram, M. B. and Thompson, T. E. (1990) Modulation of phospholipid acyl chain order by cholesterol. A solid- state 2H nuclear magnetic resonance study. Biochemistry 29, 10676–10684.

    PubMed  CAS  Google Scholar 

  68. Pilot, J. D., East, J. M., and Lee, A. G. (2001) Effects of bilayer thickness on the activity of diacylglycerol kinase of Escherichia coli. Biochemistry 40, 8188–8195.

    PubMed  CAS  Google Scholar 

  69. Cornelius, F. (2001) Modulation of Na, K-ATPase and Na-ATPase activity by phospholipids and cholesterol. I. Steady-state kinetics. Biochemistry 40, 8842–8851.

    PubMed  CAS  Google Scholar 

  70. Toyoshima, C., Nakasako, M., Nomura, H., and Ogawa, H. (2000) Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution. Nature 405, 647–655.

    PubMed  CAS  Google Scholar 

  71. Lee, A. G. (1998) How lipids interact with an intrinsic membrane protein: The case of the calcium pump. Biochim. Biophys. Acta 1376, 381–390.

    PubMed  CAS  Google Scholar 

  72. Caffrey, M., and Feigenson, G. W. (1981) Fluorescence quenching in model membranes. 3. Relationship between calcium adenosinetriphosphatase enzyme activity and the affinity of the protein for phosphatidylcholines with different acyl chain characteristics. Biochemistry 20, 1949–1961.

    PubMed  CAS  Google Scholar 

  73. Johannsson, A., Keightley, C. A., Smith, G. A., Richards, C. D., Hesketh, T. R., and Metcalfe, J. C. (1981) The effect of bilayer thickness and n-alkanes on the activity of the (Ca2++Mg2+)-dependent ATPase of sarcoplasmic reticulum. J. Biol. Chem. 256, 1643–1650.

    PubMed  CAS  Google Scholar 

  74. Starling, A. P., East, J. M., and Lee, A. G. (1993) Effects of phosphatidylcholine fatty acyl chain length on calcium binding and other functions of the (Ca2+−Mg2+)-ATPase. Biochemistry 32, 1593–1600.

    PubMed  CAS  Google Scholar 

  75. Starling, A. P., East, J. M., and Lee, A. G. (1995) Evidence that the effects of phospholipids on the activity of the Ca2+-ATPase do not involve aggregation. Biochem. J. 308, 343–346.

    PubMed  CAS  Google Scholar 

  76. Cornea, R. L., and Thomas, D. D. (1994) Effects of membrane thickness on the molecular dynamics and enzymatic activity of reconstituted Ca-ATPase. Biochemistry 33, 2912–2920.

    PubMed  CAS  Google Scholar 

  77. Harroun, T. A., Heller, W. T., Weiss, T. M., Yang, L., and Huang, H. W. (1999) Theoretical analysis of hydrophobic matching and membrane-mediated interactions in lipid bilayers containing gramicidin. Biophys. J. 76, 3176–3185.

    PubMed  CAS  Google Scholar 

  78. Huang, H. W. (1999) Peptide-lipid interactions and mechanisms of antimicrobial peptides. Novartis Found. Symp. 225, 188–200.

    Article  PubMed  CAS  Google Scholar 

  79. Palczewski, K., Kumasaka, T., Hori, T., Behnke, C. A., Motoshima, H., Fox, B. A., Le Trong, I., Teller, D. C., Okada, T., Stenkamp, R. E., Yamamoto, M., and Miyano, M. (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Sciece 289 739–745.

    CAS  Google Scholar 

  80. Krishna, A. G., Menon, S. T., Terry, T. J., and Sakmar, T. P. (2002) Evidence that helix 8 of rhodopsin acts as a membrane-dependent conformations switch. Biochemistry 41, 8298–8309.

    PubMed  CAS  Google Scholar 

  81. Mozsolits, H., Unabia, S., Ahmad, A., Morton, C. J., Thomas, W. G., and Aguilar, M. I. (2002) Electrostatic and hydrophobic forces tether the proximal region of the Angiotensin II Receptor (AT(1A)) carboxyl terminus to anionic lipids. Biochemistry 41, 7830–7840.

    PubMed  CAS  Google Scholar 

  82. Hurley, J. H., Tsujishita, Y., and Pearson, M. A. (2000) Floundering about at cell membranes: A structural view of phospholipid signaling. Curr. Opin. Struct. Biol. 10, 737–743.

    PubMed  CAS  Google Scholar 

  83. Ordway, R. W., Singer, J. J., and Walsh, J. V., Jr. (1991) Direct regulation of ion channels by fatty acids. Trends Neurosci. 14, 96–100.

    PubMed  CAS  Google Scholar 

  84. Meves, H. (1994) Modulation of ion channels by arachidonic acids. Prog. Neurobiol. 43, 175–186.

    PubMed  CAS  Google Scholar 

  85. Sechi, A. S. and Wehland, J. (2000) The actin cytoskeleton and plasma membrane connection: PtdIns(4,5)P(2) influences cytoskeletal protein activity at the plasma membrane. J. Cell Sci. 113 Pt 21, 3685–3695.

    PubMed  CAS  Google Scholar 

  86. McLaughlin, S., Wang, J., Gambhir, A., and Murray, D. (2002) PIP2 and proteins: Interactions, Organization, and Information Flow. Annu. Rev. Biophys. Biomol. Struct. 31, 151–175.

    PubMed  CAS  Google Scholar 

  87. Hannun, Y. A. and Obeid, L. M. (2002) The Ceramide-centric universe of lipid-mediated cell regulation: Stress encounters of the lipid kind. J. Biol. Chem. 277, 25847–25850.

    PubMed  CAS  Google Scholar 

  88. Spiegel, S. and Milstien, S. (2002) Sphingosine 1-phosphate, a key cell signaling molecule. J. Biol. Chem. 277, 25851–25854.

    PubMed  CAS  Google Scholar 

  89. Hurley, J. H. and Meyer, T. (2001) Subcellular targeting by membrane lipids. Curr. Opin. Cell Biol. 13, 146–152.

    PubMed  CAS  Google Scholar 

  90. Hilgemann, D. W. (1997) Cytoplasmic ATP-dependent regulation of ion transporters and channels: mechanisms and messengers. Annu. Rev. Physiol. 59, 193–220.

    PubMed  CAS  Google Scholar 

  91. Jones, J. A. and Hannun, Y. A. (2002) Fight binding inhibition of protein phosphatase-1 by phosphatidic acid. Specificity of inhibition by the phospholipid. J. Biol. Chem. 277, 15530–15538.

    PubMed  CAS  Google Scholar 

  92. Hwang, T. C., Guggino, S. E., and Guggino, W. B. (1990) Direct modulation of secretory chloride channels by arachidonic and other cis unsaturated fatty acids. Proc. Natl. Acad. Sci. USA. 87, 5706–5709.

    PubMed  CAS  Google Scholar 

  93. Schwartz, R. D. and Yu, X. (1992) Inhibition of GABA-gated chloride channel function by arachidonic acid. Brain Res. 585, 405–410.

    PubMed  CAS  Google Scholar 

  94. Ordway, R. W., Walsh, J. V., Jr., and Singer, J. J. (1989) Arachidonic acid and other fatty acids directly activate potassium channels in smooth muscle cells. Science 244, 1176–1179.

    PubMed  CAS  Google Scholar 

  95. Brown, D. A. and London, E. (1998) Functions of lipid rafts in biological membranes. Annu. Rev. Cell Dev. Biol. 14, 111–136.

    PubMed  CAS  Google Scholar 

  96. Carter, W. G. and Hakomori, S. (1981) A new cell surface, detergent-insoluble glycoprotein matrix of disulfide bonds in stabilization of the matrix. J. Biol. Chem. 256, 6953–6960.

    PubMed  CAS  Google Scholar 

  97. Okada, Y., Mugnai, G., Bremer, E. G., and Hakomori, S. (1984) Glycosphingolipids in detergent-insoluble substrate attachment matrix (DISAM) prepared from substrate attachment material (SAM). Their possible role in regulating cell adhesion. Exp. Cell Res. 155, 448–456.

    PubMed  CAS  Google Scholar 

  98. Brzustowicz, M. R., Cherezov, V., Caffrey, M., Stillwell, W., and Wassall, S. R. (2002) Molecular organization of cholesterol in polyunsaturated membranes: Microdomain formation. Biophys. J. 82, 285–298.

    PubMed  CAS  Google Scholar 

  99. Radhakrishnan, A. and McConnell, H. M. (2000) Electric field effect on cholesterol-phospholipid complexes. Proc. Natl. Acad. Sci. USA. 97, 1073–1078.

    PubMed  CAS  Google Scholar 

  100. Xu, X. and London, E. (2000) The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation. Biochemistry 39, 843–849.

    PubMed  CAS  Google Scholar 

  101. Fridricksson, E. K., Shipkova, P. A., Sheets, E. D., Holowka, D., Baird, B., and McLafferty, F. W. (1999) Quantitative analysis of phospholipids in functionally important membrane domains from RBL-2H3 mast cells using tandem high-resolution mass spectrometry. Biochemistry 38, 8056–8063.

    Google Scholar 

  102. Schneiter, R., Brugger, B., Sandhoff, R., Zellnig, G., Leber, A., Lampl, M., Athenstaedt, K., Hrastnik, C., Eder, S., Daum, G., Paltauf, F., Wieland, F. T., and Kohlwein, S. D. (1999) Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species en route to the plasma membrane. J. Cell Biol. 146, 741–754.

    PubMed  CAS  Google Scholar 

  103. Brown, R. E. (1998) Sphingolipid organization in biomembranes: What physical studies of model membranes reveal. J. Cell Sci. 111, 1–9.

    PubMed  CAS  Google Scholar 

  104. Rietveld, A. and Simons, K. (1998) The differential miscibility of lipids as the basis for the formation of functional membrane rafts. Biochim. Biophys. Acta 1376, 467–479.

    PubMed  CAS  Google Scholar 

  105. Dietrich, C., Bagatolli, L. A., Volovyk, Z. N., Thompson, N. L., Levi, M., Jacobson, K., and Gratton, E. (2001) Lipid rafts reconstituted in model membranes. Biophys. J. 80, 1417–1428.

    PubMed  CAS  Google Scholar 

  106. Moffett, S., Brown, D. A., and Linder, M. E. (2000) Lipid-dependent targeting of G proteins into rafts. J. Biol. Chem. 275, 2191–2198.

    PubMed  CAS  Google Scholar 

  107. Harder, T., Scheiffele, P., Verkade, P., and Simons, K. (1998) Lipid domain structure of the plasma membrane revealed by patching of membrane components. J. Cell Biol. 141, 929–942.

    PubMed  CAS  Google Scholar 

  108. Cheng, P. C., Dykstra, M. L., Mitchell, R. N., and Pierce, S. K. (1999) A role for lipid rafts in B cell antigen receptor signaling and antigen targeting. J. Exp. Med. 190, 1549–1560.

    PubMed  CAS  Google Scholar 

  109. Janes, P. W., Ley, S. C., and Magee, A. I. (1999) Aggregation of lipid rafts accompanies signaling via the T cell antigen receptor. J. Cell Biol. 147, 447–461.

    PubMed  CAS  Google Scholar 

  110. Anderson, R. G. (1998) The caveolae membrane system. Annu. Rev. Biochem. 67, 199–225.

    PubMed  CAS  Google Scholar 

  111. Dustin, M. L. and Shaw, A. S. (1999) Costimulation: Building an immunological synapse. Science 283, 649–650.

    PubMed  CAS  Google Scholar 

  112. Cheng, P. C., Cherukuri, A., Dykstra, M., Malapati, S., Sproul, T., Chen, M. R., and Pierce, S. K. (2001) Floating the raft hypothesis: the roles of lipid rafts in B cell antigen receptor function. Semin. Immunol. 13, 107–114.

    PubMed  CAS  Google Scholar 

  113. Cherukuri, A., Dykstra, M., and Pierce, S. K. (2001) Floating the raft hypothesis: Lipid rafts play a role in immune cell activation. Immunity 14, 657–660.

    PubMed  CAS  Google Scholar 

  114. Miceli, M. C., Moran, M., Chung, C. D., Patel, V. P., Low, T., and Zinnanti, W. (2001) Co-stimulation and counter-stimulation: Lipid raft clustering controls TCR signaling and functional outcomes. Semin. Immunol 13, 115–128.

    PubMed  CAS  Google Scholar 

  115. Simons, K. and Ikonen, E. (1997) Functional rafts in cell membranes. Nature 387, 569–572.

    PubMed  CAS  Google Scholar 

  116. Martens, J. R., Navarro-Polanco, R., Coppock, E. A., Nishiyama, A., Parshley, L., Grobaski, T. D., and Tamkun, M. M. (2000) Differential targeting of Shaker-like potassium channels to lipid rafts. J. Biol. Chem. 275, 7443–7446.

    PubMed  CAS  Google Scholar 

  117. Bruses, J. L., Chauvet, N., and Rutishauer, U. (2001) Membrane lipid rafts are necessary for the maintenance of the α7 nicotinic acetlylcholine receptor in somatic spines of ciliary neurons. J. Neurosci. 21, 504–512.

    PubMed  CAS  Google Scholar 

  118. Papazian, D. M., Schwarz, T. L., Tempel, B. L., Jan, Y. N., and Jan, L. Y. (1987) Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila. Science 237, 749–753.

    PubMed  CAS  Google Scholar 

  119. Shieh, C. C., Coghlan, M., Sullivan, J. P., and Gopalakrishnan, M. (2000) Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol. Rev. 52, 557–594.

    PubMed  CAS  Google Scholar 

  120. Choe, S. (2002) Potassium channel structures. Nat. Rev. Neurosci. 3, 115–121.

    PubMed  CAS  Google Scholar 

  121. Yellen, G. (2002) The voltage-gated potassium channels and their relatives. Nature 419, 35–42.

    PubMed  CAS  Google Scholar 

  122. MacKinnon, R., Cohen, S. L., Kuo, A., Lee, A., and Chait, B. T. (1998) Structural conservation in prokaryotic and eukaryotic potassium channels. Science 280, 106–109.

    PubMed  CAS  Google Scholar 

  123. Lu, Z., Klem, A. M., and Ramu, Y. (2001) Ion conduction pore is conserved among potassium channels. Nature 413, 809–813.

    PubMed  CAS  Google Scholar 

  124. Valiyaveetil, F. I., Zhou, Y., and MacKinnon, R. (2002) Lipids in the structure, folding, and function of the KcsA K+ channels. Biochemistry 41, 10771–10777.

    PubMed  CAS  Google Scholar 

  125. Armstrong, C. M. and Hille, B. (1998) Voltage-gated ion channels and electrical excitability. Neuron 20, 371–380.

    PubMed  CAS  Google Scholar 

  126. Yi, B. A., Minor, D. L., Jr., Lin, Y. F., Jan, Y. N., and Jan, L. Y. (2001) Controlling potassium channel activities: Interplay between the membrane and intracellular factors. Proc. Natl. Acad. Sci. USA 98, 11016–11023.

    PubMed  CAS  Google Scholar 

  127. Magoski, N. S., Wilson, G. F., and Kaczmarek, L. K. (2002) Protein kinase modulation of a neuronal cation channel requires protein- protein interactions mediated by an Src homology 3 domain. J. Neurosci. 22, 1–9.

    PubMed  CAS  Google Scholar 

  128. Dascal, N. (2001) Ion-channel regulation by G proteins. Trends Endocrinol. Metab. 12, 391–398.

    PubMed  CAS  Google Scholar 

  129. Mitchell, D. C., Niu, S. L., and Litman, B. J. (2001) Optimization of receptor-G protein coupling by bilayer lipid composition I: Kinetics of rhodopsin-transducin binding. J. Biol. Chem. 276, 42801–42806.

    PubMed  CAS  Google Scholar 

  130. Niu, S. L., Mitchell, D. C., and Litman, B. J. (2001) Optimization of receptor-G protein coupling by bilayer lipid composition II: Formation of metarhodopsin II-transducin complex. J. Biol. Chem. 276, 42807–42811.

    PubMed  CAS  Google Scholar 

  131. Hanlon, M. R., and Wallace, B. A. (2002) Structure and function of voltage-dependent ion channel regulatory beta subunits. Biochemistry 41, 2886–2894.

    PubMed  CAS  Google Scholar 

  132. Martens, J. R., Sakamoto, N., Sullivan, S. A., Grobaski, T. D., and Tamkun, M. M. (2001) Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J. Biol. Chem. 276, 8409–8414.

    PubMed  CAS  Google Scholar 

  133. Gong, J., Xu, J., Bezanilla, M., van Huizen, R., Derin, R., and Li, M. (1999) Differential stimulation of PKC phosphorylation of potassium channels by ZIP1 and ZIP2. Science 285, 1565–1569.

    PubMed  CAS  Google Scholar 

  134. Cook, K. K. and Fadool, D. A. (2002) Two adaptor proteins differentially modulate the phosphorylation and biophysics of Kv1.3 ion channel by SRC kinase. J. Biol. Chem. 277, 13268–13280.

    PubMed  CAS  Google Scholar 

  135. Jiang, Y., Lee, A., Chen, J., Cadene, M., Chait, B. T., and MacKinnon, R. (2002) Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417, 515–522.

    PubMed  CAS  Google Scholar 

  136. Petrou, S., Ordway, R. W., Hamilton, J. A., Walsh, J. V., Jr., and Singer, J. J. (1994) Structural requirements for charged lipid molecules to directly increase or suppress K+ channel activity in smooth muscle cells. Effects of fatty acids, lysophosphatidate, acyl coenzyme A and sphingosine. J. Gen. Physiol. 103, 471–486.

    PubMed  CAS  Google Scholar 

  137. Denson, D. D., Wang, X., Worrell, R. T., and Eaton, D. C. (2000) Effects of fatty acids on BK channels in GH(3) cells. Am. J. Physiol. Cell Physiol. 279, C1211–1219.

    PubMed  CAS  Google Scholar 

  138. Turnheim, K., Gruber, J., Wachter, C., and Ruiz-Gutierrez, V. (1999) Membrane phospholipid composition affects function of potassium channels from rabbit colon epithelium. Am. J. Physiol. Cell Physiol. 277, C83–90.

    CAS  Google Scholar 

  139. Jan, L. Y., and Jan, Y. N. (1997) Cloned potassium channels from eukaryotes and prokaryotes. Annu. Rev. Neurosci. 20, 91–123.

    PubMed  CAS  Google Scholar 

  140. Ruppersberg, J. P. (2000) Intracellular regulation of inward rectifier K+ channels. Pflugers Arch. 441, 1–11.

    PubMed  CAS  Google Scholar 

  141. Fakler, B., Brandle, U., Glowatzki, E., Zenner, H. P., and Ruppersberg, J. P. (1994) Kir2.1 inward rectifier K+ channels are regulated independently by protein kinases and ATP hydrolysis. Neuron 13, 1413–1420.

    PubMed  CAS  Google Scholar 

  142. Huang, C. L., Feng, S., and Hilgemann, D. W. (1998) Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbg. Nature 391, 803–806.

    PubMed  CAS  Google Scholar 

  143. Rohacs, T., Chen, J., Prestwich, G. D., and Logothetis, D. E. (1999) Distinct specificities of inwardly rectifying K+ channels for phosphoinositides. J. Biol. Chem. 274, 36065–36072.

    PubMed  CAS  Google Scholar 

  144. Lupu, V. D., Kaznacheyeva, E., Krishna, U. M., Falck, J. R., and Bezprozvanny, I. (1998) Functional coupling of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate receptor. J. Biol. Chem. 273, 14067–14070.

    PubMed  CAS  Google Scholar 

  145. Zhainazarov, A. B. and Ache, B. W. (1999) Effects of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate on a Na+-gated nonselective cation channel. J. Neurosci. 19, 2929–2937.

    PubMed  CAS  Google Scholar 

  146. Ma, H. P., Saxena, S., and Warnock, D. G. (2002) Anionic phospholipids regulate native and expressed epithelial sodium channel (ENaC). J. Biol. Chem. 277, 7641–7644.

    PubMed  CAS  Google Scholar 

  147. Inagaki, N., Gonoi, T., Clement, J. P. t., Namba, N., Inazawa, J., Gonzalez, G., et al. (1995) Reconstitution of IKATP: An inward rectifier subunit plus the sulfonylurea receptor. Science 270, 1166–1170.

    PubMed  CAS  Google Scholar 

  148. Baukrowitz, T. and Fakler, B. (2000) KATP channels gated by intracellular nucleotides and phospholipids. Eur. J. Biochem. 267, 5842–5848.

    PubMed  CAS  Google Scholar 

  149. Fink, M., Lesage, F., Duprat, F., Heurteaux, C., Reyes, R., Fosset, M., and Lazdunski, M. (1998) A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J. 17, 3297–3308.

    PubMed  CAS  Google Scholar 

  150. Patel, A. J., Honore, E., Maingret, F., Lesage, F., Fink, M., Duprat, F., and Lazdunski, M. (1998) A mammalian two pore domain mechano-gated S-like K+ channel. EMBO J. 17, 4283–4290.

    PubMed  CAS  Google Scholar 

  151. Maingret, F., Patel, A. J., Lesage, F., Lazdunski, M., and Honore, E. (2000) Lysophospholipids open the two-pore domain mechano-gated K+ channels TREK-1 and TRAAK. J. Biol. Chem. 275, 10128–10133.

    PubMed  CAS  Google Scholar 

  152. Lesage, F., Terrenoire, C., Romey, G., and Lazdunski, M. (2000) Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. J. Biol. Chem. 275, 28398–28405.

    PubMed  CAS  Google Scholar 

  153. Arias, H. R. (1997) Topology of ligand binding sites on the nicotinic acetylcholine receptor. Brain Res. Brain Res. Rev. 25, 133–191.

    PubMed  CAS  Google Scholar 

  154. Corringer, P. J., Le Novere, N., and Changeux, J. P. (2000) Nicotinic receptors at the amino acid level. Annu. Rev. Pharmacol. Toxicol. 40, 431–458.

    PubMed  CAS  Google Scholar 

  155. Legendre, P. (2001) The glycinergic inhibitory synapse. Cell Mol. Life Sci. 58, 760–93.

    PubMed  CAS  Google Scholar 

  156. Karlin, A. (2002) Emerging structure of the nicotinic acetylcholine receptors. Nat. Rev. Neurosci. 3, 102–114.

    PubMed  CAS  Google Scholar 

  157. Fong, T. M. and McNamee, M. G. (1986) Correlation between acetylcholine receptor function and structural properties of membranes. Biochemistry 25, 830–840.

    PubMed  CAS  Google Scholar 

  158. Criado, M., Eibl, H., and Barrantes, F. J. (1984) Functional properties of the acetylcholine receptor incorporated in model lipid membranes. Differential effects of chain length and head group of phospholipids on receptor affinity states and receptor- mediated ion translocation. J. Biol. Chem. 259, 9188–9198.

    PubMed  CAS  Google Scholar 

  159. Ochoa, E. L., Dalziel, A. W., and McNamee, M. G. (1983) Reconstitution of acetylcholine receptor function in lipid vesicles of defined composition. Biochim. Biophys. Acta 727, 151–162.

    PubMed  CAS  Google Scholar 

  160. Criado, M., Eibl, H., and Barrantes, F. J. (1982) Effects of lipids on acetylcholine receptor. Essential need of cholesterol for maintenance of agonist-induced state transitions in lipid vesicles. Biochemistry 21, 3622–3629.

    PubMed  CAS  Google Scholar 

  161. Jones, O. T., Eubanks, J. H., Earnest J. P., and McNamee, M. G. (1988) A minimum number of lipids are required to support the functional properties of the nicotinic acetylcholine receptor. Biochemistry 27, 3733–3742.

    PubMed  CAS  Google Scholar 

  162. Ellena, J. F., Blazing, M. A., and McNamee, M. G. (1983) Lipid-protein interactions in reconstituted membranes containing acetylcholine receptor. Biochemistry 22, 5523–5535.

    PubMed  CAS  Google Scholar 

  163. Antollini, S. S., Soto, M. A., Bonini de Romanelli, I., Gutierrez-Merino, C., Sotomayor, P., and Barrantes, F. J. (1996) Physical state of bulk and protein-associated lipid in nicotinic acetylcholine receptor-rich membrane studied by laurdan generalized polarization and fluorescence energy transfer. Biophys. J. 70, 1275–1284.

    PubMed  CAS  Google Scholar 

  164. Barrantes, F. The lipid annulus of the nicotinic acetylcholine receptor as a locus of structural-functional interactions. In: A. Watts, ed. Protein-Lipid Interactions, Elsevier Science Publishers B.V., 1993:231–256.

  165. Bhushan, A. and McNamee, M. G. (1990) Differential scanning calorimetry and Fourier transform infrared analysis of lipid-protein interactions involving the nicotinic acetylcholine receptor. Biochim. Biophys. Acta 1027, 93–101.

    PubMed  CAS  Google Scholar 

  166. Narayanaswami, V. and McNamee, M. G. (1993) Protein-lipid interactions and Torpedo californica nicotinic acetylcholine receptor function. 2. Membrane fluidity and ligand-mediated alteration in the accessibility of gamma subunit cysteine residues to cholesterol. Biochemistry 32, 12420–12427.

    PubMed  CAS  Google Scholar 

  167. Dreger, M., Krauss, M., Herrmann, A., and Hucho, F. (1997) Interactions of the nicotinic acetylcholine receptor transmembrane segments with the lipid bilayer in native receptor-rich membranes. Biochemistry 36, 839–847.

    PubMed  CAS  Google Scholar 

  168. Raines, D. E. and Miller, K. W. (1993) The role of charge in lipid selectivity for the nicotinic acetylcholine receptor. Biophys. J. 64, 632–641.

    PubMed  CAS  Google Scholar 

  169. Sunshine, C. and McNamee, M. G. (1992) Lipid modulation of nicotinic acetylcholine receptor function: The role of neutral and negatively charged lipids. Biochim. Biophys. Acta 1108, 240–246.

    PubMed  CAS  Google Scholar 

  170. Bhushan A. and McNamee M. G. (1993) Correlation of phospholipid structure with functional effects on the nicotinic acetylcholine receptor. A modulatory role for phosphatidic acid. Biophys. J. 64, 716–723.

    PubMed  CAS  Google Scholar 

  171. Leibel, W. S., Firestone, L. L., Legler, D. C., Braswell, L. M., and Miller, K. W. (1987) Two pools of cholesterol in acetylcholine receptor-rich membranes from Torpedo. Biochim. Biophys. Acta 897, 249–260.

    PubMed  CAS  Google Scholar 

  172. Jones, O. T. and McNamee, M. G. (1988) Annular and nonannular binding sites for cholesterol associated with the nicotinic acetylcholine receptor. Biochemistry 27, 2364–2374.

    PubMed  CAS  Google Scholar 

  173. Antollini, S. S. and Barrantes, F. J. (1998) Disclosure of discrete sites for phospholipid and sterols at the protein-lipid interface in native acetylcholine receptor-rich membrane. Biochemistry 37, 16653–16662.

    PubMed  CAS  Google Scholar 

  174. Fernandez, A. M., Fernandez-Ballester, G., Ferragut, J. A., and Gonzalez-Ros, J. M. (1993) Labeling of the nicotinic acetylcholine receptor by a photoactivatable steroid probe: Effects of cholesterol and cholinergic ligands. Biochim. Biophys. Acta 1149, 135–144.

    PubMed  CAS  Google Scholar 

  175. Corbin, J., Wang, H. H., and Blanton, M. P. (1998) Identifying the cholesterol binding domain in the nicotinic acetylcholine receptor with [125I]azido-cholesterol. Biochim. Biophys. Acta 1414, 65–74.

    PubMed  CAS  Google Scholar 

  176. Addona, G. H., Sandermann, H., Jr., Kloczewiak, M. A., Husain, S. S., and Miller, K. W. (1998) Where does cholesterol act during activation of the nicotinic acetylcholine receptor? Biochim. Biophys. Acta 1370, 299–309.

    PubMed  CAS  Google Scholar 

  177. Barrantes, F. J., Antollini, S. S., Blanton, M. P., and Prieto, M. (2000) Topography of nicotinic acetylcholine receptor membrane-embededded domains. J. Biol. Chem. 275, 37333–37339.

    PubMed  CAS  Google Scholar 

  178. Popot, J. L., Demel, R. A., Sobel, A., Van Deenen, L. L., and Changeux, J. P. (1978) Interaction of the acetylcholine (nicotinic) receptor protein from Torpedo marmorata electric organ with monolayers of pure lipids. Eur. J. Biochem. 85, 27–42.

    PubMed  CAS  Google Scholar 

  179. Kilian, P. L., Dunlap, C. R., Mueller, P., Schell, M. A., Huganir, R. L., and Racker, E. (1980) Reconstitution of acetylcholine receptor from Torpedo californica with highly purified phospholipids: Effect of alpha-tocopherol, phylloquinone, and other terpenoid quinones. Biochem. Biophys. Res. Commun. 93, 409–414.

    PubMed  CAS  Google Scholar 

  180. Rotstein, N. P., Arias, H. R., Barrantes, F. J., and Aveldano, M. I. (1987) Composition of lipids in elasmobranch electric organ and acetylcholine receptor membranes. J. Neurochem. 49, 1333–1340.

    PubMed  CAS  Google Scholar 

  181. Sunshine, C. and McNamee, M. G. (1994) Lipid modulation of nicotinic acetylcholine receptor function: The role of membrane lipid composition and fluidity. Biochim. Biophys. Acta 1191, 59–64.

    PubMed  CAS  Google Scholar 

  182. Baenziger, J. E., Morris, M. L., Darsaut, T. E., and Ryan, S. E. (2000) Effect of membranelipid composition on the conformational equilibria of the nicotinic acetylcholine receptor. J. Biol. Chem. 275, 777–784.

    PubMed  CAS  Google Scholar 

  183. Ryan, S. E., Demers, C. N., Chew, J. P., and Baenziger, J. E. (1996) Structural effects of neutral and anionic lipids on the nicotinic acetylcholine receptor. An infrared difference spectroscopy study. J. Biol. Chem. 271, 24590–24597.

    PubMed  CAS  Google Scholar 

  184. Firestone, L. L., Alifimoff, J. K., and Miller, K. W. (1994) Does general anesthetic-induced desensitization of the Torpedo acetylcholine receptor correlate with lipid disordering? Mol. Pharmacol. 46, 508–515.

    PubMed  CAS  Google Scholar 

  185. Fernandez-Ballester, G., Castresana, J., Fernandez, A. M., Arrondo, J. L., Ferragut, J. A., and Gonzalez-Ros, J. M. (1994) A role for cholesterol as a structural effector of the nicotinic acetylcholine receptor. Biochemistry 33, 4065–4071.

    PubMed  CAS  Google Scholar 

  186. Fong, T. M. and McNamee, M. G. (1987) Stabilization of acetylcholine receptor secondary structure by cholesterol and negatively charged phospholipids in membranes. Biochemistry 26, 3871–3880.

    PubMed  CAS  Google Scholar 

  187. Butler, D. H. and McNamee, M. G. (1993) FTIR analysis of nicotinic acetylcholine receptor secondary structure in reconstituted membranes. Biochim. Biophys. Acta 1150, 17–24.

    PubMed  CAS  Google Scholar 

  188. Methot, N., Demers, C. N., and Baenziger, J. E. (1995) Structure of both the ligand- and lipid-dependent channel-inactive states of the nicotinic acetylcholine receptor probed by FTIR spectroscopy and hydrogen exchange. Biochemistry 34, 15142–15149.

    PubMed  CAS  Google Scholar 

  189. McCarthy, M. P., and Stroud, R. M. (1989) Changes in conformation upon agonist binding, and nonequivalent labeling, of the membrane-spanning regions of the nicotinic acetylcholine receptor subunits. J. Biol. Chem. 264, 10911–10916.

    PubMed  CAS  Google Scholar 

  190. McCarthy, M. P. and Moore, M. A. (1992) Effects of lipids and detergents on the conformation of the nicotinic acetylcholine receptor from Torpedo californica. J. Biol. Chem. 267, 7655–7663.

    PubMed  CAS  Google Scholar 

  191. Rankin, S. E., Addona, G. H., Kloczewiak, M. A., Bugge, B., and Miller, K. W. (1997) The cholesterol dependence of activation and fast desensitization of the nicotinic acetylcholine receptor. Biophys. J. 73, 2446–2455.

    Article  PubMed  CAS  Google Scholar 

  192. Raines, D. E. and Krishnan, N. S. (1998) Agonist binding and affinity state transitions in reconstituted nicotinic acetylcholine receptors revealed by single and sequential mixing stopped-flow fluorescence spectroscopies. Biochim. Biophys. Acta 1374, 83–93.

    PubMed  CAS  Google Scholar 

  193. Sooksawate, T. and Simmonds, M. A. (2001) Effects of membrane cholesterol on the sensitivity of the GABAA receptor to GABA in acutely dissociated rat hippocampal neurones. Neuropharmacology 40, 178–184.

    PubMed  CAS  Google Scholar 

  194. Sooksawate, T. and Simmonds, M. A. (2001) Influence of membrane cholesterol on modulation of the GABAA receptor by neuroactive steroids and other potentiators. Br. J. Pharmacol. 134, 1303–1311.

    PubMed  CAS  Google Scholar 

  195. Sooksawate, T. and Simmonds, M. A. (1998) Increased membrane cholesterol reduces the potentiation of GABAA currents by neurosteroids in dissociated hippocampal neurones. Neuropharmacology 37, 1103–1110.

    PubMed  CAS  Google Scholar 

  196. Scanlon, S. M., Williams, D. C., and Schloss, P. (2001) Membrane cholesterol modulates serotonin transporter activity. Biochemistry 40, 10507–10513.

    PubMed  CAS  Google Scholar 

  197. Gulbins, E., Szabo, I., Baltzer, K., and Lang, F. (1997) Ceramide-induced inhibition of T lymphocyte voltage-gated potassium channel is mediated by tyrosine kinases. Proc. Natl. Acad. Sci. USA. 94, 7661–7666.

    PubMed  CAS  Google Scholar 

  198. Hilgemann, D. W. and Ball, R. (1996) Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2. Science 273, 956–959.

    PubMed  CAS  Google Scholar 

  199. Fan, Z. and Makielski, J. C. (1997) Anionic phospholipids activate ATP-sensitive potassium channels. J. Biol. Chem. 272, 5388–5395.

    PubMed  CAS  Google Scholar 

  200. Shyng, S. L. and Nichols, C. G. (1998) Membrane phospholipid control of nucleotide sensitivity of KATP channels. Science 282, 1138–1141.

    PubMed  CAS  Google Scholar 

  201. Baukrowitz, T., Schulte, U., Oliver, D., Herlitze, S., Krauter, T., Tucker, S. J., Ruppersberg, J. P., and Fakler, B. (1998) PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science 282, 1141–1144.

    PubMed  CAS  Google Scholar 

  202. Krauter, T., Ruppersberg, J. P., and Baukrowitz, T (2001) Phospholipids as modulators of KATP channels: distinct mechanisms for control of sensitivity to sulphonylureas, K+ channel openers, and ATP. Mol. Pharmacol. 59, 1086–1093.

    PubMed  CAS  Google Scholar 

  203. MacGregor, G. G., Dong, K., Vanoye, C. G., Tang, L., Giebisch, G., and Hebert, S. C. (2002) Nucleotides and phospholipids compete for binding to the C terminus of KATP channels. Proc. Natl. Acad. Sci. USA. 99, 2726–2731.

    PubMed  CAS  Google Scholar 

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    Tommy S. Tillman & Michael Cascio

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Tillman, T.S., Cascio, M. Effects of membrane lipids on ion channel structure and function. Cell Biochem Biophys 38, 161–190 (2003). https://doi.org/10.1385/CBB:38:2:161

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