Wang2008_Rilusole_SkeletalMuscleCells

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Short description

This a model from the article:
Riluzole-induced block of voltage-gated Na+ current and activation of BKCa channels in cultured differentiated human skeletal muscle cells.
Wang YJ, Lin MW, Lin AA, Wu SN. Life Sci. (2008) 82(1-2) pp 11-20; Pubmed ID: 18068197 ,
Abstract:
Riluzole is known to be of therapeutic use in the management of amyotrophic lateral sclerosis. In this study, we investigated the effects of riluzole on ion currents in cultured differentiated human skeletal muscle cells (dHSkMCs). Western blotting revealed the protein expression of alpha-subunits for both large-conductance Ca2+-activated K+ (BK(Ca)) channel and Na+ channel (Na(v)1.5) in these cells. Riluzole could reduce the frequency of spontaneous beating in dHSkMCs. In whole-cell configuration, riluzole suppressed voltage-gated Na+ current (I(Na)) in a concentration-dependent manner with an IC50 value of 2.3 microM. Riluzole (10 microM) also effectively increased Ca2+-activated K+ current (I(K(Ca))) which could be reversed by iberiotoxin (200 nM) and paxilline (1 microM), but not by apamin (200 nM). In inside-out patches, when applied to the inside of the cell membrane, riluzole (10 microM) increased BK(Ca)-channel activity with a decrease in mean closed time. Simulation studies also unraveled that both decreased conductance of I(Na) and increased conductance of I(K(Ca)) utilized to mimic riluzole actions in skeletal muscle cells could combine to decrease the amplitude of action potentials and increase the repolarization of action potentials. Taken together, inhibition of I(Na) and stimulation of BK(Ca)-channel activity caused by this drug are partly, if not entirely, responsible for its muscle relaxant actions in clinical setting.

This model was taken from the CellML repository and automatically converted to SBML.
The original model was: Wang_Lin_Lin_Wu, 1999, version02
The original CellML model was created by:
Nunns, Geoffrey, Rogan
gnunns1(at)jhem.jhu.edu
The University of Auckland
Auckland Bioengineering Institute

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Format
SBML (L2V3)
Related Publication
  • Riluzole-induced block of voltage-gated Na+ current and activation of BKCa channels in cultured differentiated human skeletal muscle cells.
  • Wang YJ, Lin MW, Lin AA, Wu SN
  • Life sciences , 1/ 2008 , Volume 82 , pages: 11-20
  • Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
  • Riluzole is known to be of therapeutic use in the management of amyotrophic lateral sclerosis. In this study, we investigated the effects of riluzole on ion currents in cultured differentiated human skeletal muscle cells (dHSkMCs). Western blotting revealed the protein expression of alpha-subunits for both large-conductance Ca2+-activated K+ (BK(Ca)) channel and Na+ channel (Na(v)1.5) in these cells. Riluzole could reduce the frequency of spontaneous beating in dHSkMCs. In whole-cell configuration, riluzole suppressed voltage-gated Na+ current (I(Na)) in a concentration-dependent manner with an IC50 value of 2.3 microM. Riluzole (10 microM) also effectively increased Ca2+-activated K+ current (I(K(Ca))) which could be reversed by iberiotoxin (200 nM) and paxilline (1 microM), but not by apamin (200 nM). In inside-out patches, when applied to the inside of the cell membrane, riluzole (10 microM) increased BK(Ca)-channel activity with a decrease in mean closed time. Simulation studies also unraveled that both decreased conductance of I(Na) and increased conductance of I(K(Ca)) utilized to mimic riluzole actions in skeletal muscle cells could combine to decrease the amplitude of action potentials and increase the repolarization of action potentials. Taken together, inhibition of I(Na) and stimulation of BK(Ca)-channel activity caused by this drug are partly, if not entirely, responsible for its muscle relaxant actions in clinical setting.
Contributors
Vijayalakshmi Chelliah

Metadata information

is
BioModels Database MODEL7817907010
isDescribedBy
PubMed 18068197
hasTaxon
Taxonomy Homo sapiens
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
isVersionOf
Human Disease Ontology amyotrophic lateral sclerosis
Gene Ontology response to drug
occursIn
Brenda Tissue Ontology skeletal muscle
Curation status
Non-curated
Original model(s)
http://www.cellml.org/models/wang_lin_lin_wu_2008_version02
  • Model originally submitted by : Vijayalakshmi Chelliah
  • Submitted: Mar 23, 2009 4:51:45 PM
  • Last Modified: Mar 23, 2009 4:51:45 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Mar 23, 2009 4:51:45 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Current version of Wang2008_Rilusole_SkeletalMuscleCells
  • Version: 1 public model Download this version
    • Submitted on: Mar 23, 2009 4:51:45 PM
    • Submitted by: Vijayalakshmi Chelliah
    • With comment: Original import of Wang2008_Rilusole_SkeletalMuscleCells