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MODEL7817907010 - Wang2008_Rilusole_SkeletalMuscleCells


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Reference Publication
Publication ID: 18068197
Wang YJ, Lin MW, Lin AA, Wu SN.
Riluzole-induced block of voltage-gated Na+ current and activation of BKCa channels in cultured differentiated human skeletal muscle cells.
Life Sci. 2008 Jan; 82(1-2): 11-20
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.  [more]
Original Model: CellML logo
Submitter: Vijayalakshmi Chelliah
Submission Date: 23 Mar 2009 16:51:45 UTC
Last Modification Date: 23 Mar 2009 16:51:45 UTC
Creation Date: 23 Mar 2009 16:51:45 UTC
bqbiol:occursIn Brenda Tissue Ontology skeletal muscle
bqbiol:hasTaxon Taxonomy Homo sapiens
bqbiol:isVersionOf Gene Ontology response to drug
Human Disease Ontology amyotrophic lateral sclerosis

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 ,
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
The University of Auckland
Auckland Bioengineering Institute

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