Suh2004_KCNQ_Regulation

  public model
Short description

The model reproduces FIG 11A and FIG 11B of the paper. However, please note that FIG 11B is a plot of normalised amounts versus time. The "stoichiometry" field has been used to convert fluxes from membrane species to volume species. The value of 0.0009967 is a product of (Surface to Volume_M*(1/Avagadro's number)*1E21. 0.6 is the surface to volume ratio of the plasma membrane, 1E21 is required for a unit surface to volume ratio and the Avagadro's number is present in the denominator to convert molecules to moles. The model was successfully tested using MathSBML and SBML ODESolver.
All the kinetic laws have the unit items per second , which requires the one reaction taking place in the cytoplasm - IP3Phosphatase - to include an explicit conversion factor both in the kinetic law and the stoichiometry of IP3_C . The kinetic law is multiplied and the stoichiometry divided by the number of molecules per micro-mole. This conversion factor is only required for correct units and can be replaced by 1, if it should lead to numerical problems.


To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L3V1)
Related Publication
  • Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq.
  • Suh BC, Horowitz LF, Hirdes W, Mackie K, Hille B
  • The Journal of general physiology , 6/ 2004 , Volume 123 , Issue 6 , pages: 663-683
  • Department of Physiology and Biophysics, University of Washington School of Medicine, G-424 Health Sciences Building, Box 357290, Seattle, WA 98195-7290, USA.
  • Receptor-mediated modulation of KCNQ channels regulates neuronal excitability. This study concerns the kinetics and mechanism of M1 muscarinic receptor-mediated regulation of the cloned neuronal M channel, KCNQ2/KCNQ3 (Kv7.2/Kv7.3). Receptors, channels, various mutated G-protein subunits, and an optical probe for phosphatidylinositol 4,5-bisphosphate (PIP2) were coexpressed by transfection in tsA-201 cells, and the cells were studied by whole-cell patch clamp and by confocal microscopy. Constitutively active forms of Galphaq and Galpha11, but not Galpha13, caused a loss of the plasma membrane PIP2 and a total tonic inhibition of the KCNQ current. There were no further changes upon addition of the muscarinic agonist oxotremorine-M (oxo-M). Expression of the regulator of G-protein signaling, RGS2, blocked PIP2 hydrolysis and current suppression by muscarinic stimulation, confirming that the Gq family of G-proteins is necessary. Dialysis with the competitive inhibitor GDPbetaS (1 mM) lengthened the time constant of inhibition sixfold, decreased the suppression of current, and decreased agonist sensitivity. Removal of intracellular Mg2+ slowed both the development and the recovery from muscarinic suppression. When combined with GDPbetaS, low intracellular Mg2+ nearly eliminated muscarinic inhibition. With nonhydrolyzable GTP analogs, current suppression developed spontaneously and muscarinic inhibition was enhanced. Such spontaneous suppression was antagonized by GDPbetaS or GTP or by expression of RGS2. These observations were successfully described by a kinetic model representing biochemical steps of the signaling cascade using published rate constants where available. The model supports the following sequence of events for this Gq-coupled signaling: A classical G-protein cycle, including competition for nucleotide-free G-protein by all nucleotide forms and an activation step requiring Mg2+, followed by G-protein-stimulated phospholipase C and hydrolysis of PIP2, and finally PIP2 dissociation from binding sites for inositol lipid on the channels so that KCNQ current was suppressed. Further experiments will be needed to refine some untested assumptions.
Contributors
Harish Dharuri, Krishna Kumar Tiwari

Metadata information

is
BioModels Database MODEL4662889298
KEGG Pathway Calcium signaling pathway
BioModels Database BIOMD0000000081
KEGG Pathway Phosphatidylinositol signaling system
BioModels Database MODEL4662889298
BioModels Database BIOMD0000000081
isDescribedBy
PubMed 15173220
hasTaxon
Taxonomy Homo sapiens

Curation status
Curated

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  • Model originally submitted by : Harish Dharuri
  • Submitted: Nov 27, 2006 10:15:44 PM
  • Last Modified: May 16, 2019 10:14:25 AM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: May 16, 2019 10:14:25 AM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Automatically added model identifier BIOMD0000000081
  • Version: 2 public model Download this version
    • Submitted on: Jul 5, 2012 5:29:50 PM
    • Submitted by: Harish Dharuri
    • With comment: Current version of Suh2004_KCNQ_Regulation
  • Version: 1 public model Download this version
    • Submitted on: Nov 27, 2006 10:15:44 PM
    • Submitted by: Harish Dharuri
    • With comment: Original import of Suh2004_KCNQ_Regulation
Curator's comment:
(added: 29 Sep 2009, 16:00:48, updated: 29 Sep 2009, 16:00:48)
Reproduction of fig 11 A and B from the original publication using SBML ODESolver.