Wang2008 - Mimicking the inhibitory effect of riluzole on membrane conductance in skeletal fibres
This model is described in the article:
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.
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To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.
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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 , Issue 1-2 , pages: 11-20 , PubMed ID: 18068197
- 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.
Submitter of this revision: administrator
Modellers: administrator, Vijayalakshmi Chelliah
Metadata information
isDescribedBy (3 statements)
hasTaxon (1 statement)
hasInstance (9 statements)
KEGG Drug Riluzole (JAN/USP/INN)
ModelDB 105528
Taxonomy Homo sapiens
Human Disease Ontology amyotrophic lateral sclerosis
Gene Ontology voltage-gated channel activity
Gene Ontology action potential
BioModels Database MODEL7817907010
isVersionOf (3 statements)
Gene Ontology response to drug
Human Disease Ontology amyotrophic lateral sclerosis
hasPart (1 statement)
occursIn (1 statement)
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000693_url.xml | SBML L2V4 representation of Wang2008 - Mimicking the inhibitory effect of riluzole on membrane conductance in skeletal fibres | 74.97 KB | Preview | Download |
Additional files |
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| BIOMD0000000693-biopax2.owl | Auto-generated BioPAX (Level 2) | 7.81 KB | Preview | Download |
| BIOMD0000000693-biopax3.owl | Auto-generated BioPAX (Level 3) | 10.49 KB | Preview | Download |
| BIOMD0000000693.m | Auto-generated Octave file | 12.47 KB | Preview | Download |
| BIOMD0000000693.pdf | Auto-generated PDF file | 163.57 KB | Preview | Download |
| BIOMD0000000693.png | Auto-generated Reaction graph (PNG) | 4.27 KB | Preview | Download |
| BIOMD0000000693.sci | Auto-generated Scilab file | 154.00 Bytes | Preview | Download |
| BIOMD0000000693.svg | Auto-generated Reaction graph (SVG) | 845.00 Bytes | Preview | Download |
| BIOMD0000000693.vcml | Auto-generated VCML file | 900.00 Bytes | Preview | Download |
| BIOMD0000000693.xpp | Auto-generated XPP file | 9.24 KB | Preview | Download |
| BIOMD0000000693_urn.xml | Auto-generated SBML file with URNs | 74.93 KB | Preview | Download |
| MODEL7817907010.cps | Curated model COPASI file. | 103.93 KB | Preview | Download |
| MODEL7817907010.sedml | SED-ML file for figure 6A | 1.64 KB | Preview | Download |
- Model originally submitted by : Vijayalakshmi Chelliah
- Submitted: Mar 23, 2009 4:51:45 PM
- Last Modified: Mar 21, 2018 4:49:54 PM
Revisions
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Version: 3
- Submitted on: Mar 21, 2018 4:49:54 PM
- Submitted by: administrator
- With comment: Notes updated using online editor.
-
Version: 2
- Submitted on: Mar 23, 2009 4:51:45 PM
- Submitted by: Vijayalakshmi Chelliah
- With comment: Current version of Wang2008_Rilusole_SkeletalMuscleCells
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Version: 1
- Submitted on: Mar 23, 2009 4:51:45 PM
- Submitted by: Vijayalakshmi Chelliah
- With comment: Original import of Wang2008_Rilusole_SkeletalMuscleCells
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| o | 0.1 mmol |
| IKCa calcium-activated potassium channel activity |
-0.0716677369048711 mmol |
| IL | 0.0 mmol |
| alpha h | 0.467439960739393 mmol |
| alpha n | 0.00543709940740284 mmol |
| jserca | 0.06 mmol |
| Vm Membrane Potential |
-75.0 mmol |
| d | 0.0 mmol |
| alpha m | 0.262861215247374 mmol |
| ICa | 0.0 mmol |
| Reactions | Rate | Parameters |
|---|---|---|
| o = (ooinf-o)/tau | (ooinf-o)/tau | ooinf = 0.013131127960815; tau = 3.69947662338091 |
| IKCa = gKca*o*w*(Vm-EK) | [] | EK = -70.0; gKca = 0.5 |
| IL = gL_max*(Vm-EL) | [] | gL_max = 0.0024; EL = -75.0 |
| alpha_h = alpha_h_max*exp((Eh-Vm)/v_alpha_m) | [] | alpha_h_max = 0.0156; v_alpha_m = 10.0; Eh = -41.0 |
| alpha_n = alpha_n_max*(Vm-En)/(1-exp((En-Vm)/v_alpha_n)) | [] | En = -40.0; v_alpha_n = 7.0; alpha_n_max = 0.0229 |
| jserca = kserca*c | [] | kserca = 0.4 |
| Vm = (Stimulus-(INa+ICa+IK+IL+IT+IKCa))/Cm | (Stimulus-(INa+ICa+IK+IL+IT+IKCa))/Cm | Cm = 0.009 |
| d = (1-d)*alphad-d*betad | (1-d)*alphad-d*betad | alphad = 8.05558916679958E-5; betad = 0.00696831163375364 |
| alpha_m = alpha_m_max*(Vm-Em)/(1-exp((Em-Vm)/v_alpha_m)) | [] | alpha_m_max = 0.208; v_alpha_m = 10.0; Em = -42.0 |
| ICa = gca*d^2 | [] | gca = -3.75057964796293 |
(added: 21 Mar 2018, 16:51:13, updated: 21 Mar 2018, 16:51:13)