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Divergent effects of anesthetics on lipid bilayer properties and sodium channel function

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Abstract

General anesthetics revolutionized medicine by allowing surgeons to perform more complex and much longer procedures. This widely used class of drugs is essential to patient care, yet their exact molecular mechanism(s) are incompletely understood. One early hypothesis over a century ago proposed that nonspecific interactions of anesthetics with the lipid bilayer lead to changes in neuronal function via effects on membrane properties. This model was supported by the Meyer–Overton correlation between anesthetic potency and lipid solubility and despite more recent evidence for specific protein targets, in particular ion-channels, lipid bilayer-mediated effects of anesthetics is still under debate. We therefore tested a wide range of chemically diverse general anesthetics on lipid bilayer properties using a sensitive and functional gramicidin-based assay. None of the tested anesthetics altered lipid bilayer properties at clinically relevant concentrations. Some anesthetics did affect the bilayer, though only at high supratherapeutic concentrations, which are unlikely relevant for clinical anesthesia. These results suggest that anesthetics directly interact with membrane proteins without altering lipid bilayer properties at clinically relevant concentrations. Voltage-gated Na+ channels are potential anesthetic targets and various isoforms are inhibited by a wide range of volatile anesthetics. They inhibit channel function by reducing peak Na+ current and shifting steady-state inactivation toward more hyperpolarized potentials. Recent advances in crystallography of prokaryotic Na+ channels, which are sensitive to volatile anesthetics, together with molecular dynamics simulations and electrophysiological studies will help identify potential anesthetic interaction sites within the channel protein itself.

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References

  • Andersen OS (2008) Perspectives on how to drug an ion channel. J Gen Physiol 131:395–397

    Article  PubMed  PubMed Central  Google Scholar 

  • Andersen OS, Koeppe RE (2007) Bilayer thickness and membrane protein function: an energetic perspective. Annu Rev Biophys Biomol Struct 36:107–130

    Article  CAS  PubMed  Google Scholar 

  • Andersen OS, Sawyer DB, Koeppe R (1992) Modulation of channel function by the host bilayer. In: Bruce PG, Easwaran KRK (eds) Biomembrane structure and function: the state of the art. Adenine Press, Schenectady, NY

    Google Scholar 

  • Artigas P, Al’aref SJ, Hobart EA, Diaz LF, Sakaguchi M, Straw S, Andersen OS (2006) 2,3-butanedione monoxime affects cystic fibrosis transmembrane conductance regulator channel function through phosphorylation-dependent and phosphorylation-independent mechanisms: the role of bilayer material properties. Mol Pharmacol 70:2015–2026

    Article  CAS  PubMed  Google Scholar 

  • Ashrafuzzaman M, Lampson M, Greathouse D, Koeppe Ii R, Andersen O (2006) Manipulating lipid bilayer material properties using biologically active amphipathic molecules. J Phys Condens Matter 18:S1235

    Article  CAS  Google Scholar 

  • Barber AF, Carnevale V, Klein ML, Eckenhoff RG, Covarrubias M (2014) Modulation of a voltage-gated Na+ channel by sevoflurane involves multiple sites and distinct mechanisms. Proc Natl Acad Sci USA 111:6726–6731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bean BP, Shrager P, Goldstein DA (1981) Modification of sodium and potassium channel gating kinetics by ether and halothane. J Gen Physiol 77:233–253

    Article  CAS  PubMed  Google Scholar 

  • Bernard C (1878) Leçons sur les Phénoménes de la Vie Communs aux Animaux et aux Végétaux. Baillière, Paris

  • Bienvenüe A, Marie JS (1994) Chapter 12—modulation of protein function by lipids. In: Dick H (ed) Current topics in membranes, vol 40. Academic Press, Cambridge, pp 319–354

    Google Scholar 

  • Bigelow HJ (1846) Insensibility during surgical operations produced by inhalation. Boston Medi Surg J 35:309–317

    Article  Google Scholar 

  • Brown MF (1994) Modulation of rhodopsin function by properties of the membrane bilayer. Chem Phys Lipids 73:159–180

    Article  CAS  PubMed  Google Scholar 

  • Bruno MJ, Koeppe RE, Andersen OS (2007) Docosahexaenoic acid alters bilayer elastic properties. Proc Natl Acad Sci USA 104:9638–9643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruno MJ, Rusinova R, Gleason NJ, Koeppe RE 2nd, Andersen OS (2013) Interactions of drugs and amphiphiles with membranes: modulation of lipid bilayer elastic properties by changes in acyl chain unsaturation and protonation. Faraday Discuss 161:461–480 (discussion 563–489)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cantor RS (1997) The lateral pressure profile in membranes: a physical mechanism of general anesthesia. Biochemistry 36:2339–2344

    Article  CAS  PubMed  Google Scholar 

  • Dickinson R, Peterson BK, Banks P, Simillis C, Martin JC, Valenzuela CA, Maze M, Franks NP (2007) Competitive inhibition at the glycine site of the N-methyl-d-aspartate receptor by the anesthetics xenon and isoflurane: evidence from molecular modeling and electrophysiology. Anesthesiology 107:756–767

    Article  CAS  PubMed  Google Scholar 

  • Dilger JP (1981) The thickness of monoolein lipid bilayers as determined from reflectance measurements. Biochim Biophys Acta 645:357–363

    Article  CAS  PubMed  Google Scholar 

  • Dilger JP, Fisher LR, Haydon DA (1982) A critical comparison of electrical and optical methods for bilayer thickness determination. Chem Phys Lipid 30:159–176

    Article  CAS  Google Scholar 

  • Elliott JR, Needham D, Dilger JP, Haydon DA (1983) The effects of bilayer thickness and tension on gramicidin single-channel lifetime. Biochim Biophys Acta 735:95–103

    Article  CAS  PubMed  Google Scholar 

  • Elliott JR, Haydon DA, Hendry BM, Needham D (1985) Inactivation of the sodium current in squid giant axons by hydrocarbons. Biophys J 48:617–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans E, Needham D (1987) Physical properties of surfactant bilayer membranes: thermal transitions, elasticity, rigidity, cohesion and colloidal interactions. J Phys Chem 91:4219–4228

    Article  CAS  Google Scholar 

  • Evans E, Rawicz W, Hofmann A (1995) Lipid bilayer expansion and mechanical disruption in solutions of water-soluble bile acid Falk Symposium. Kluwer Academic Publication, Hingham, p 59

    Google Scholar 

  • Fettiplace R, Andrews DM, Haydon DA (1971) The thickness, composition and structure of some lipid bilayers and natural membranes. J Membr Biol 5:277–296

    Article  CAS  PubMed  Google Scholar 

  • Franks NP, Lieb WR (1979) The structure of lipid bilayers and the effects of general anaesthetics. An x-ray and neutron diffraction study. J Mol Biol 133:469–500

    Article  CAS  PubMed  Google Scholar 

  • Goulian M, Mesquita ON, Fygenson DK, Nielsen C, Andersen OS, Libchaber A (1998) Gramicidin channel kinetics under tension. Biophys J 74:328–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gray E, Karslake J, Machta BB, Veatch SL (2013) Liquid general anesthetics lower critical temperatures in plasma membrane vesicles. Biophys J 105:2751–2759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gray EM, Diaz-Vazquez G, Veatch SL (2015) Growth conditions and cell cycle phase modulate phase transition temperatures in RBL-2H3 derived plasma membrane vesicles. PLoS One 10:e0137741

    Article  PubMed  PubMed Central  Google Scholar 

  • Gruner SM, Shyamsunder E (1991) Is the mechanism of general anesthesia related to lipid membrane spontaneous curvature? Ann N Y Acad Sci 625:685–697

    Article  CAS  PubMed  Google Scholar 

  • Harris RA, Bruno P (1985) Effects of ethanol and other intoxicant-anesthetics on voltage-dependent sodium channels of brain synaptosomes. J Pharmacol Exp Ther 232:401–406

    CAS  PubMed  Google Scholar 

  • Haseneder R, Kratzer S, Kochs E, Eckle VS, Zieglgansberger W, Rammes G (2008) Xenon reduces N-methyl-d-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated synaptic transmission in the amygdala. Anesthesiology 109:998–1006

    Article  CAS  PubMed  Google Scholar 

  • Haydon DA, Urban BW (1983a) The action of alcohols and other non-ionic surface active substances on the sodium current of the squid giant axon. J Physiol 341:411–427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haydon DA, Urban BW (1983b) The action of hydrocarbons and carbon tetrachloride on the sodium current of the squid giant axon. J Physiol 338:435–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haydon DA, Urban BW (1983c) The effects of some inhalation anaesthetics on the sodium current of the squid giant axon. J Physiol 341:429–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helfrich P, Jakobsson E (1990) Calculation of deformation energies and conformations in lipid membranes containing gramicidin channels. Biophys J 57:1075–1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemmings HC Jr, Akabas MH, Goldstein PA, Trudell JR, Orser BA, Harrison NL (2005) Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol Sci 26:503–510

    Article  CAS  PubMed  Google Scholar 

  • Herold KF, Hemmings HC Jr (2012) Sodium channels as targets for volatile anesthetics. Front Pharmacol 3:50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herold KF, Nau C, Ouyang W, Hemmings HC (2009) Isoflurane inhibits the tetrodotoxin-resistant voltage-gated sodium channel Nav1.8. Anesthesiology 111:591–599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herold KF, Sanford RL, Lee W, Schultz MF, Ingolfsson HI, Andersen OS, Hemmings HC Jr (2014) Volatile anesthetics inhibit sodium channels without altering bulk lipid bilayer properties. J Gen Physiol 144:545–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herold KF, Sanford RL, Lee W, Andersen OS, Hemmings HC, Jr (2017) Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties. Proc Natl Acad Sci USA 114(12):3109–3114. doi:10.1073/pnas.1611717114

    Article  CAS  PubMed  Google Scholar 

  • Hille B (1977) Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515

    Article  CAS  PubMed  Google Scholar 

  • Howard RJ, Trudell JR, Harris RA (2014) Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics. Pharmacol Rev 66:396–412

    Article  PubMed  PubMed Central  Google Scholar 

  • Howery AE, Elvington S, Abraham SJ, Choi KH, Dworschak-Simpson S, Phillips S, Ryan CM, Sanford RL, Almqvist J, Tran K, Chew TA, Zachariae U, Andersen OS, Whitelegge J, Matulef K, Du Bois J, Maduke MC (2012) A designed inhibitor of a CLC antiporter blocks function through a unique binding mode. Chem Biol 19:1460–1470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang HW (1986) Deformation free energy of bilayer membrane and its effect on gramicidin channel lifetime. Biophys J 50:1061–1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang TC, Koeppe RE 2nd, Andersen OS (2003) Genistein can modulate channel function by a phosphorylation-independent mechanism: importance of hydrophobic mismatch and bilayer mechanics. Biochemistry 42:13646–13658

    Article  CAS  PubMed  Google Scholar 

  • Ingólfsson HI, Koeppe RE 2nd, Andersen OS (2007) Curcumin is a modulator of bilayer material properties. Biochemistry 46:10384–10391

    Article  PubMed  Google Scholar 

  • Ingólfsson HI, Thakur P, Herold KF, Hobart EA, Ramsey NB, Periole X, de Jong DH, Zwama M, Yilmaz D, Hall K, Maretzky T, Hemmings HC Jr, Blobel C, Marrink SJ, Kocer A, Sack JT, Andersen OS (2014) Phytochemicals perturb membranes and promiscuously alter protein function. ACS Chem Biol 9:1788–1798

    Article  PubMed  PubMed Central  Google Scholar 

  • Jackson MB (1989) Perfection of a synaptic receptor: kinetics and energetics of the acetylcholine receptor. Proc Natl Acad Sci USA 86:2199–2203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kendig JJ, Courtney KR, Cohen EN (1979) Anesthetics: molecular correlates of voltage- and frequency-dependent sodium channel block in nerve. J Pharmacol Exp Ther 210:446–452

    CAS  PubMed  Google Scholar 

  • Kinde MN, Bondarenko V, Granata D, Bu W, Grasty KC, Loll PJ, Carnevale V, Klein ML, Eckenhoff RG, Tang P, Xu Y (2016) Fluorine-19 NMR and computational quantification of isoflurane binding to the voltage-gated sodium channel NaChBac. Proc Natl Acad Sci USA 113:13762–13767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee AG (2004) How lipids affect the activities of integral membrane proteins. Biochim Biophys Acta 1666:62–87

    Article  CAS  PubMed  Google Scholar 

  • Lundbæk JA, Andersen OS (1994) Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers. J Gen Physiol 104:645–673

    Article  PubMed  Google Scholar 

  • Lundbæk JA, Andersen OS (1999) Spring constants for channel-induced lipid bilayer deformations. Estimates using gramicidin channels. Biophys J 76:889–895

    Article  PubMed  PubMed Central  Google Scholar 

  • Lundbæk JA, Birn P, Girshman J, Hansen AJ, Andersen OS (1996) Membrane stiffness and channel function. Biochemistry 35:3825–3830

    Article  PubMed  Google Scholar 

  • Lundbaek JA, Maer AM, Andersen OS (1997) Lipid bilayer electrostatic energy, curvature stress, and assembly of gramicidin channels. Biochemistry 36:5695–5701

    Article  CAS  PubMed  Google Scholar 

  • Lundbæk JA, Birn P, Hansen AJ, Søgaard R, Nielsen C, Girshman J, Bruno MJ, Tape SE, Egebjerg J, Greathouse DV, Mattice GL, Koeppe RE, Andersen OS (2004) Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol. J Gen Physiol 123:599–621

    Article  PubMed  PubMed Central  Google Scholar 

  • Lundbæk JA, Birn P, Tape SE, Toombes GES, Søgaard R, Koeppe RE, Gruner SM, Hansen AJ, Andersen OS (2005) Capsaicin regulates voltage-dependent sodium channels by altering lipid bilayer elasticity. Mol Pharmacol 68:680–689

    PubMed  Google Scholar 

  • Lundbaek JA, Collingwood SA, Ingolfsson HI, Kapoor R, Andersen OS (2010a) Lipid bilayer regulation of membrane protein function: gramicidin channels as molecular force probes. J R Soc Interface 7:373–395

    Article  CAS  PubMed  Google Scholar 

  • Lundbæk JA, Koeppe RE 2nd, Andersen OS (2010b) Amphiphile regulation of ion channel function by changes in the bilayer spring constant. Proc Natl Acad Sci USA 107:15427–15430

    Article  PubMed  PubMed Central  Google Scholar 

  • Machta BB, Gray E, Nouri M, McCarthy NL, Gray EM, Miller AL, Brooks NJ, Veatch SL (2016) Conditions that stabilize membrane domains also antagonize n-alcohol anesthesia. Biophys J 111:537–545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marsh D (2007) Lateral pressure profile, spontaneous curvature frustration, and the incorporation and conformation of proteins in membranes. Biophys J 93:3884–3899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer H (1899) Zur theorie der alkoholnarkose. Arch Exp Pathol Pharmakol 42:109–118

    Article  Google Scholar 

  • Mondal S, Khelashvili G, Shan J, Andersen OS, Weinstein H (2011) Quantitative modeling of membrane deformations by multihelical membrane proteins: application to G-protein coupled receptors. Biophys J 101:2092–2101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monod J, Wyman J, Changeux JP (1965) On the nature of allosteric transitions: a plausible model. J Mol Biol 12:88–118

    Article  CAS  PubMed  Google Scholar 

  • Mouritsen OG, Bloom M (1984) Mattress model of lipid-protein interactions in membranes. Biophys J 46:141–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nielsen C, Goulian M, Andersen OS (1998) Energetics of inclusion-induced bilayer deformations. Biophys J 74:1966–1983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikonorov IM, Blanck TJ, Recio-Pinto E (1998) The effects of halothane on single human neuronal L-type calcium channels. Anesth Analg 86:885–895

    Article  CAS  PubMed  Google Scholar 

  • O’Connell AM, Koeppe RE 2nd, Andersen OS (1990) Kinetics of gramicidin channel formation in lipid bilayers: transmembrane monomer association. Science 250:1256–1259

    Article  PubMed  Google Scholar 

  • Ouyang W, Hemmings H (2007) Isoform-selective effects of isoflurane on voltage-gated Na+ channels. Anesthesiology 107:91–98

    Article  CAS  PubMed  Google Scholar 

  • Ouyang W, Wang G, Hemmings H (2003) Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminals. Mol Pharmacol 64:373–381

    Article  CAS  PubMed  Google Scholar 

  • Ouyang W, Jih T, Zhang T, Correa A, Hemmings H (2007) Isoflurane inhibits NaChBac, a prokaryotic voltage-gated sodium channel. J Pharmacol Exp Ther 322:1076–1083

    Article  CAS  PubMed  Google Scholar 

  • Ouyang W, Herold KF, Hemmings HC (2009) Comparative effects of halogenated inhaled anesthetics on voltage-gated Na+ channel function. Anesthesiology 110:582–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Overton C (1901) Studien über die Narkose zugleich ein Beitrag zur allgemeinen Pharmakologie. Verlag von Gustav Fischer, Jena

    Google Scholar 

  • Patel AJ, Honore E (2001) Anesthetic-sensitive 2P domain K+ channels. Anesthesiology 95:1013–1021

    Article  CAS  PubMed  Google Scholar 

  • Payandeh J, Scheuer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature 475:353–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perouansky M (2012) The quest for a unified model of anesthetic action: a century in Claude Bernard’s shadow. Anesthesiology 117:465–474

    Article  PubMed  Google Scholar 

  • Purtell K, Gingrich KJ, Ouyang W, Herold KF, Hemmings HC Jr (2015) Activity-dependent depression of neuronal sodium channels by the general anaesthetic isoflurane. Br J Anaesth 115:112–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raju SG, Barber AF, LeBard DN, Klein ML, Carnevale V (2013) Exploring volatile general anesthetic binding to a closed membrane-bound bacterial voltage-gated sodium channel via computation. PLoS Comput Biol 9:e1003090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ratnakumari L, Hemmings H (1998) Inhibition of presynaptic sodium channels by halothane. Anesthesiology 88:1043–1054

    Article  CAS  PubMed  Google Scholar 

  • Rehberg B, Xiao YH, Duch DS (1996) Central nervous system sodium channels are significantly suppressed at clinical concentrations of volatile anesthetics. Anesthesiology 84:1223–1233 (discussion 1227A)

    Article  CAS  PubMed  Google Scholar 

  • Ren D, Navarro B, Xu H, Yue L, Shi Q, Clapham DE (2001) A prokaryotic voltage-gated sodium channel. Science 294:2372–2375

    Article  CAS  PubMed  Google Scholar 

  • Rudolph U, Antkowiak B (2004) Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 5:709–720

    Article  CAS  PubMed  Google Scholar 

  • Rusinova R, Herold KF, Sanford RL, Greathouse DV, Hemmings HC Jr, Andersen OS (2011) Thiazolidinedione insulin sensitizers alter lipid bilayer properties and voltage-dependent sodium channel function: implications for drug discovery. J Gen Physiol 138:249–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rusinova R, Koeppe RE 2nd, Andersen OS (2015) A general mechanism for drug promiscuity: studies with amiodarone and other antiarrhythmics. J Gen Physiol 146:463–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sand RM, Gingrich KJ, Macharadze T, Herold KF, Hemmings HC Jr (2017) Isoflurane modulates activation and inactivation gating of the prokaryotic Na+ channel NaChBac. J Gen Physiol 149(6):623–638. doi:10.1085/jgp.201611600

    Article  PubMed  Google Scholar 

  • Sawyer DB, Koeppe RE 2nd, Andersen OS (1989) Induction of conductance heterogeneity in gramicidin channels. Biochemistry 28:6571–6583

    Article  CAS  PubMed  Google Scholar 

  • Shiraishi M, Harris R (2004) Effects of alcohols and anesthetics on recombinant voltage-gated Na+ channels. J Pharmacol Exp Ther 309:987–994

    Article  CAS  PubMed  Google Scholar 

  • Sirois JE, Lynch C 3rd, Bayliss DA (2002) Convergent and reciprocal modulation of a leak K+ current and I(h) by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones. J Physiol 541:717–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Søgaard R, Werge TM, Bertelsen C, Lundbye C, Madsen KL, Nielsen CH, Lundbæk JA (2006) GABA(A) receptor function is regulated by lipid bilayer elasticity. Biochemistry 45:13118–13129

    Article  PubMed  Google Scholar 

  • Sonner JM, Cantor RS (2013) Molecular mechanisms of drug action: an emerging view. Annu Rev Biophys 42:143–167

    Article  CAS  PubMed  Google Scholar 

  • Stadnicka A, Kwok WM, Hartmann HA, Bosnjak ZJ (1999) Effects of halothane and isoflurane on fast and slow inactivation of human heart hH1a sodium channels. Anesthesiology 90:1671–1683

    Article  CAS  PubMed  Google Scholar 

  • Study RE (1994) Isoflurane inhibits multiple voltage-gated calcium currents in hippocampal pyramidal neurons. Anesthesiology 81:104–116

    Article  CAS  PubMed  Google Scholar 

  • Suchyna TM, Tape SE, Koeppe RE 2nd, Andersen OS, Sachs F, Gottlieb PA (2004) Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers. Nature 430:235–240

    Article  CAS  PubMed  Google Scholar 

  • Sula A, Booker J, Ng LC, Naylor CE, DeCaen PG, Wallace BA (2017) The complete structure of an activated open sodium channel. Nat Commun 8:14205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tibbs GR, Rowley TJ, Sanford RL, Herold KF, Proekt A, Hemmings HC Jr, Andersen OS, Goldstein PA, Flood PD (2013) HCN1 channels as targets for anesthetic and nonanesthetic propofol analogs in the amelioration of mechanical and thermal hyperalgesia in a mouse model of neuropathic pain. J Pharmacol Exp Ther 345:363–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Veatch SL, Keller SL (2005a) Miscibility phase diagrams of giant vesicles containing sphingomyelin. Phys Rev Lett 94:148101

    Article  PubMed  Google Scholar 

  • Veatch SL, Keller SL (2005b) Seeing spots: complex phase behavior in simple membranes. Biochim Biophys Acta 1746:172–185

    Article  CAS  PubMed  Google Scholar 

  • White SH (1977) Studies of the physical chemistry of planar bilayer membranes using high-precision measurements of specific capacitance. Ann N Y Acad Sci 303:243–265

    CAS  PubMed  Google Scholar 

  • Yokoyama T, Minami K, Sudo Y, Horishita T, Ogata J, Yanagita T, Uezono Y (2011) Effects of sevoflurane on voltage-gated sodium channel Na(v)1.8, Na(v)1.7, and Na(v)1.4 expressed in Xenopus oocytes. J Anesth 25:609–613

    Article  PubMed  Google Scholar 

  • Zhelev DV (1998) Material property characteristics for lipid bilayers containing lysolipid. Biophys J 75:321–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zimmerman SA, Jones MV, Harrison NL (1994) Potentiation of gamma-aminobutyric acidA receptor Cl− current correlates with in vivo anesthetic potency. J Pharmacol Exp Ther 270:987–991

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) Grant HE4554/5-1 (K.F.H.), National Institutes of Health Grants GM058055 (to H.C.H.) and GM021347 (to O.S.A.).

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Authors and Affiliations

  1. Department of Anesthesiology, Weill Cornell Medicine, New York, NY, 10065, USA

    Karl F. Herold & Hugh C. Hemmings Jr.

  2. Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, 10065, USA

    Olaf S. Andersen

  3. Department of Pharmacology, Weill Cornell Medicine, New York, NY, 10065, USA

    Hugh C. Hemmings Jr.

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  1. Karl F. Herold
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  3. Hugh C. Hemmings Jr.
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Correspondence to Hugh C. Hemmings Jr..

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Special Issue: Shining Light on Membrane Proteins.

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Herold, K.F., Andersen, O.S. & Hemmings, H.C. Divergent effects of anesthetics on lipid bilayer properties and sodium channel function. Eur Biophys J 46, 617–626 (2017). https://doi.org/10.1007/s00249-017-1239-1

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