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


: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.


Biophys J


Biophysical journal


Lee DK,Albershardt DJ,Cantor RS




Has Abstract


2015-03-10 00:00:00














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    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


    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


    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


    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


    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


    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


    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


    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


    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.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    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.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


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

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

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: McIntosh TJ,Magid AD,Simon SA

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sánchez G,Hidalgo C,Donoso P

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Tenchov B,Koynova R,Rapp G

    更新日期:2001-04-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Lundbaek JA,Andersen OS

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    pub_type: 杂志文章



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    journal_title:Biophysical journal

    pub_type: 杂志文章


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

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    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...

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    pub_type: 杂志文章


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

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    pub_type: 杂志文章


    authors: Tranchina D,Sneyd J,Cadenas ID

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    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....

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Wagner M,Timmer J

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

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    journal_title:Biophysical journal

    pub_type: 杂志文章


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

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Fischer MR,Hoff AJ

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: White SH

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Everts S,Davis JH

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    pub_type: 杂志文章


    authors: Dasika MS,Burgard A,Maranas CD

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    journal_title:Biophysical journal

    pub_type: 杂志文章


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

    更新日期:1996-06-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Vilar JM

    更新日期:2010-10-20 00:00:00