Exploring the mechanism of general anesthesia: kinetic analysis of GABAA receptor electrophysiology.

Abstract:

:A kinetic model of the effect of agonist and anesthetics on ligand-gated ion channels, developed in earlier work, is further refined and used to predict traces observed in fast-perfusion electrophysiological studies on recombinant GABAA receptors under a wide range of agonist and/or anesthetic concentrations. The model incorporates only three conformational states (resting, open, and desensitized) but allows for the modulation of the conformational free energy landscape connecting these states resulting from adsorption of agonist and/or anesthetic to the bilayer in which the protein is embedded. The model is shown to reproduce the diverse and complex features of experimental traces remarkably well, including both anesthetic-induced and agonist-induced traces, as well as the modulation of agonist-induced traces by anesthetic, either coapplied or continuously present. The solutions to the kinetic equations, which give the time-dependence of each of the nine protein states (three ligation states for each of the three conformations), describe the flow of probability among these states and thus reveal the kinetic underpinnings of the traces. Many of the parameters in the model, such as the desorption rate constants of anesthetic and agonist, are directly related to model-independent experimental measurements and thus can serve as a definitive test of its validity.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Lee DK,Albershardt DJ,Cantor RS

doi

10.1016/j.bpj.2014.12.052

subject

Has Abstract

pub_date

2015-03-10 00:00:00

pages

1081-93

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(15)00060-0

journal_volume

108

pub_type

杂志文章
  • UVA generates pyrimidine dimers in DNA directly.

    abstract::There is increasing evidence that UVA radiation, which makes up approximately 95% of the solar UV light reaching the Earth's surface and is also commonly used for cosmetic purposes, is genotoxic. However, in contrast to UVC and UVB, the mechanisms by which UVA produces various DNA lesions are still unclear. In additio...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2008.10.030

    authors: Jiang Y,Rabbi M,Kim M,Ke C,Lee W,Clark RL,Mieczkowski PA,Marszalek PE

    更新日期:2009-02-01 00:00:00

  • Dependence of DNA polymerase replication rate on external forces: a model based on molecular dynamics simulations.

    abstract::Molecular dynamics simulations are presented for a Thermus aquaticus (Taq) DNA polymerase I complex (consisting of the protein, the primer-template DNA strands, and the incoming nucleotide) subjected to external forces. The results obtained with a force applied to the DNA template strand provide insights into the effe...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.103.039313

    authors: Andricioaei I,Goel A,Herschbach D,Karplus M

    更新日期:2004-09-01 00:00:00

  • Deuterium solid-state NMR investigations of exchange labeled oriented purple membranes at different hydration levels.

    abstract::Oriented purple membranes were equilibrated under controlled (2)H(2)O relative humidity ranging from 15% to 93% and introduced into the magnetic field of an NMR spectrometer with the membrane normal parallel to the magnetic field direction. Deuterium solid-state NMR spectra of these samples resolved four deuteron popu...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(03)74480-4

    authors: Bechinger B,Weik M

    更新日期:2003-07-01 00:00:00

  • Growing actin networks form lamellipodium and lamellum by self-assembly.

    abstract::Many different cell types are able to migrate by formation of a thin actin-based cytoskeletal extension. Recently, it became evident that this extension consists of two distinct substructures, designated lamellipodium and lamellum, which differ significantly in their kinetic and kinematic properties as well as their b...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.108.134817

    authors: Huber F,Käs J,Stuhrmann B

    更新日期:2008-12-15 00:00:00

  • A new technique for calculating individual dermal fibroblast contractile forces generated within collagen-GAG scaffolds.

    abstract::Cell-mediated contraction plays a critical role in many physiological and pathological processes, notably organized contraction during wound healing. Implantation of an appropriately formulated (i.e., mean pore size, chemical composition, degradation rate) three-dimensional scaffold into an in vivo wound site effectiv...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.106.095471

    authors: Harley BA,Freyman TM,Wong MQ,Gibson LJ

    更新日期:2007-10-15 00:00:00

  • Compressibilities and volume fluctuations of archaeal tetraether liposomes.

    abstract::Bipolar tetraether lipids (BTLs) are abundant in crenarchaeota, which thrive in both thermophilic and nonthermophilic environments, with wide-ranging growth temperatures (4-108°C). BTL liposomes can serve as membrane models to explore the role of BTLs in the thermal stability of the plasma membrane of crenarchaeota. I...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2010.09.061

    authors: Chong PL,Sulc M,Winter R

    更新日期:2010-11-17 00:00:00

  • Diffusion of the second messengers in the cytoplasm acts as a variability suppressor of the single photon response in vertebrate phototransduction.

    abstract::The single photon response in vertebrate phototransduction is highly reproducible despite a number of random components of the activation cascade, including the random activation site, the random walk of an activated receptor, and its quenching in a random number of steps. Here we use a previously generated and tested...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.114058

    authors: Bisegna P,Caruso G,Andreucci D,Shen L,Gurevich VV,Hamm HE,DiBenedetto E

    更新日期:2008-05-01 00:00:00

  • Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.

    abstract::K(ATP) channels are comprised of a pore-forming protein, Kir6.x, and the sulfonylurea receptor, SURx. Interaction of adenine nucleotides with Kir6.2 positively charged amino acids such as K185 and R201 on the C-terminus causes channel closure. Substitution of these amino acids with other positively charged residues ha...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(03)74847-4

    authors: Ribalet B,John SA,Weiss JN

    更新日期:2003-01-01 00:00:00

  • Substrate chemistry-dependent conformations of single laminin molecules on polymer surfaces are revealed by the phase signal of atomic force microscopy.

    abstract::The conformation of single laminin molecules adsorbed on synthetic substrates is directly observed making use of the phase magnitude in tapping mode atomic force microscopy (AFM). With AFM, it is not possible to differentiate the proteins on the substrate if use is made of the height signal, since the roughness of the...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.106.102491

    authors: Rodríguez Hernández JC,Salmerón Sánchez M,Soria JM,Gómez Ribelles JL,Monleón Pradas M

    更新日期:2007-07-01 00:00:00

  • Water Distribution within Wild-Type NRas Protein and Q61 Mutants during Unrestrained QM/MM Dynamics.

    abstract::Point mutations in p21ras are associated with ∼30% of human tumors by disrupting its GTP hydrolysis cycle, which is critical to its molecular switch function in cellular signaling pathways. In this work, we investigate the impact of Gln 61 substitutions in the structure of the p21N-ras active site and particularly foc...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2018.07.042

    authors: Tichauer RH,Favre G,Cabantous S,Landa G,Hemeryck A,Brut M

    更新日期:2018-10-16 00:00:00

  • Repulsive interactions between uncharged bilayers. Hydration and fluctuation pressures for monoglycerides.

    abstract::Pressure versus distance relations have been obtained for solid (gel) and neat (liquid-crystalline) phase uncharged lipid bilayers by the use of x-ray diffraction analysis of osmotically stressed monoglyceride aqueous dispersions and multilayers. For solid phase monoelaidin bilayers, the interbilayer repulsive pressur...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(89)82888-7

    authors: McIntosh TJ,Magid AD,Simon SA

    更新日期:1989-05-01 00:00:00

  • Kinetic studies of calcium-induced calcium release in cardiac sarcoplasmic reticulum vesicles.

    abstract::Fast Ca(2+) release kinetics were measured in cardiac sarcoplasmic reticulum vesicles actively loaded with Ca(2+). Release was induced in solutions containing 1.2 mM free ATP and variable free [Ca(2+)] and [Mg(2+)]. Release rate constants (k) were 10-fold higher at pCa 6 than at pCa 5 whereas Ryanodine binding was hig...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(03)75037-1

    authors: Sánchez G,Hidalgo C,Donoso P

    更新日期:2003-04-01 00:00:00

  • New ordered metastable phases between the gel and subgel phases in hydrated phospholipids.

    abstract::Formation of low-temperature ordered gel phases in several fully hydrated phosphatidylethanolamines (PEs) and phosphatidylcholines (PCs) with saturated chains as well as in dipalmitoylphosphatidylglycerol (DPPG) was observed by synchrotron x-ray diffraction, microcalorimetry, and densitometry. The diffraction patterns...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(01)76157-7

    authors: Tenchov B,Koynova R,Rapp G

    更新日期:2001-04-01 00:00:00

  • Spring constants for channel-induced lipid bilayer deformations. Estimates using gramicidin channels.

    abstract::Hydrophobic interactions between a bilayer and its embedded membrane proteins couple protein conformational changes to changes in the packing of the surrounding lipids. The energetic cost of a protein conformational change therefore includes a contribution from the associated bilayer deformation energy (DeltaGdef0), w...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(99)77252-8

    authors: Lundbaek JA,Andersen OS

    更新日期:1999-02-01 00:00:00

  • Changes in quantum yield of photosynthesis in the red alga Porphyridium cruentum caused by stepwise reduction in the intensity of light preferentially absorbed by the phycobilins.

    abstract::This paper describes the relation between the quantum yield of photosynthesis in the red alga Porphyridium cruentum, and the spectral composition of light, changed by filtering white light through aqueous phycobilin solutions of increasing optical density. At sufficiently high densities of the filter solution, no meas...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/s0006-3495(60)86876-2

    authors: THOMAS JB,GOVINDJEE

    更新日期:1960-09-01 00:00:00

  • Spontaneous-curvature theory of clathrin-coated membranes.

    abstract::Clathrin-coated membranes are precursors to coated vesicles in the receptor-mediated endocytic pathway. In this paper we present a physical model for the first steps of the transformation of a clathrin-coated membrane into a coated vesicle. The theory is based on in vitro cytoplasmic acidification experiments of Heuse...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(98)77993-7

    authors: Mashl RJ,Bruinsma RF

    更新日期:1998-06-01 00:00:00

  • Asymmetric GUVs prepared by MβCD-mediated lipid exchange: an FCS study.

    abstract::We report a simple method to obtain stable asymmetric giant unilamellar vesicles (GUVs). Fluorescence correlation spectroscopy was used to quantitatively characterize vesicle properties. After brain sphingomyelin (bSM) was exchanged into dioleoylphosphatidylcholine (DOPC) GUVs, lateral diffusion in the bSM-containing ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2010.11.051

    authors: Chiantia S,Schwille P,Klymchenko AS,London E

    更新日期:2011-01-05 00:00:00

  • Molecular dynamics simulation of dipalmitoylphosphatidylcholine membrane with cholesterol sulfate.

    abstract::Using the molecular dynamics simulation technique, we studied the changes occurring in a dipalmitoylphosphatidylcholine (DPPC):cholesterol (CH) membrane at 50 mol% sterol when cholesterol is replaced with cholesterol sulfate (CS). Our simulations were performed at constant pressure and temperature on a nanosecond time...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(00)76719-1

    authors: Smondyrev AM,Berkowitz ML

    更新日期:2000-04-01 00:00:00

  • Physical characteristics of mouse sperm nuclei.

    abstract::The nuclei of epididymal sperm, isolated from C57BL/6J and CBA/J inbred mice by their resistance to trypsin digestion, retain the shape differences of the intact sperm head. Various physical characteristics of these nuclei were measured and compared. The measurement of the projected dimensions of nuclei showed that th...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(76)85730-X

    authors: Wyrobek AJ,Meistrich ML,Furrer R,Bruce WR

    更新日期:1976-07-01 00:00:00

  • Light adaptation in turtle cones. Testing and analysis of a model for phototransduction.

    abstract::Light adaptation in cones was characterized by measuring the changes in temporal frequency responses to sinusoidal modulation of light around various mean levels spanning a range of four log units. We have shown previously that some aspects of cone adaptation behavior can be accounted for by a biochemical kinetic mode...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(91)82045-8

    authors: Tranchina D,Sneyd J,Cadenas ID

    更新日期:1991-07-01 00:00:00

  • Monolayers of a model anesthetic-binding membrane protein: formation, characterization, and halothane-binding affinity.

    abstract::hbAP0 is a model membrane protein designed to possess an anesthetic-binding cavity in its hydrophilic domain and a cation channel in its hydrophobic domain. Grazing incidence x-ray diffraction shows that hbAP0 forms four-helix bundles that are vectorially oriented within Langmuir monolayers at the air-water interface....

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.105.072348

    authors: Churbanova IY,Tronin A,Strzalka J,Gog T,Kuzmenko I,Johansson JS,Blasie JK

    更新日期:2006-05-01 00:00:00

  • Gating of cyclic nucleotide-gated (CNGA1) channels by cGMP jumps and depolarizing voltage steps.

    abstract::We expressed rod-type homotetrameric cyclic nucleotide-gated (CNGA1) channels in Xenopus oocytes and studied activation by photolysis-induced jumps of the 3',5'-cyclic guanosine monophosphate (cGMP) concentration and by voltage steps. cGMP jumps to increasing concentrations up to the EC50 value of 46.5 microM decelera...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.105.078667

    authors: Nache V,Kusch J,Hagen V,Benndorf K

    更新日期:2006-05-01 00:00:00

  • The effects of non-identifiability on testing for detailed balance in aggregated Markov models for ion-channel gating.

    abstract::Aggregated Markov models are a widely used tool to model patch clamp data measured from single ion channels. These channels must obey the principle of detailed balance in thermodynamic equilibrium; otherwise, the channel is driven by an external source of energy. We investigate the power of a likelihood ratio test for...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(00)76529-5

    authors: Wagner M,Timmer J

    更新日期:2000-12-01 00:00:00

  • Effects of different cations on the hydrodynamic radius of DNA.

    abstract::The effects of different cations on the hydrodynamic radius (RH) of a 48-bp synthetic DNA are measured by time-resolved fluorescence polarization anisotropy of intercalated ethidium. Relative statistical errors in RH are only approximately 1%. With increasing cation concentration, Na+ causes a small decrease in RH, Cs...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(94)80481-3

    authors: Fujimoto BS,Miller JM,Ribeiro NS,Schurr JM

    更新日期:1994-07-01 00:00:00

  • On the long-wavelength component of the light-harvesting complex of some photosynthetic bacteria.

    abstract::The effect of the presence of a minor antenna component in light-harvesting complexes of photosynthetic bacteria is investigated with numerical simulation employing the transition probability matrix method. A model antenna system of hexagonal symmetry is adopted, using as a working hypothesis that the minor component ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(92)81689-2

    authors: Fischer MR,Hoff AJ

    更新日期:1992-10-01 00:00:00

  • Formation of "solvent-free" black lipid bilayer membranes from glyceryl monooleate dispersed in squalene.

    abstract::A simple technique for forming "black" lipid bilayer membranes containing negligible amounts of alkyl solvent is described. The membranes are formed by the method of Mueller et al (Circulation. 1962. 26:1167.) from glyceryl monooleate (GMO) dispersed in squalene. The squalene forms an annulus to satisfy the boundary c...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(78)85453-8

    authors: White SH

    更新日期:1978-09-01 00:00:00

  • 1H and (13)C NMR of multilamellar dispersions of polyunsaturated (22:6) phospholipids.

    abstract::The polyunsaturated fatty acid docosahexaenoic acid (DHA) makes up approximately 50% of the lipid chains in the retinal rod outer segment disk membranes and a large fraction of the lipid chains in the membranes of neuronal tissues. There is an extensive literature concerned with the dietary requirements for essential ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(00)76344-2

    authors: Everts S,Davis JH

    更新日期:2000-08-01 00:00:00

  • A computational framework for the topological analysis and targeted disruption of signal transduction networks.

    abstract::In this article, optimization-based frameworks are introduced for elucidating the input-output structure of signaling networks and for pinpointing targeted disruptions leading to the silencing of undesirable outputs in therapeutic interventions. The frameworks are demonstrated on a large-scale reconstruction of a sign...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.105.069724

    authors: Dasika MS,Burgard A,Maranas CD

    更新日期:2006-07-01 00:00:00

  • Near-infrared spectra of Scapharca homodimeric hemoglobin: characterization of the deoxy and photodissociated derivatives.

    abstract::The near-infrared charge transfer band at 760 nm (band III) has been investigated in deoxy and photodissociated dimeric Scapharca hemoglobin. At 300 K, the 10-ns spectrum of the carbonmonoxy derivative photoproduct is shifted by about 6 nm toward longer wavelengths with respect to the deoxy spectrum, both in buffer an...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(96)79862-4

    authors: Huang J,Leone M,Boffi A,Friedman JM,Chiancone E

    更新日期:1996-06-01 00:00:00

  • Accurate prediction of gene expression by integration of DNA sequence statistics with detailed modeling of transcription regulation.

    abstract::Gene regulation involves a hierarchy of events that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. The effects of DNA sequence on these processes have typically been studied based either on its quantitative connection with single-domain binding free energies or ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2010.08.006

    authors: Vilar JM

    更新日期:2010-10-20 00:00:00