concentration of extracellular potassium
L-type calcium current activation variable
time constant for transfer of calcium-bound ADP from subspace to myoplasm
resting myoplasmic magnesium-bound ATP concentration in normal conditions
concentration of calcium in network sarcoplasmic reticulum
concentration of magnesium-bound myoplasmic ATP
modified calcium uptake flux into network sarcoplasmic reticulum by SERCA pumps
ryanodine receptor PC1 - PO1 rate constant
magnesium-bound ADP flux from subspace to myoplasm
calcium half-saturation constant for magnesium-bound subspace ATP
maximum time-independent potassium current conductance
magnesium-bound ATP flux from subspace to myoplasm
rapid potassium current activation variable
ryanodine receptor PO1 - PC1 rate constant
time constant for transfer of calcium-bound ATP from subspace to myoplasm
maximum sarcolemmal calcium pump current
calcium permeability of L-type calcium channel
concentration of magnesium-bound myoplasmic ADP
concentration of free myoplasmic calcium
saturation factor of sodium-calcium exchanger current
maximum ATP-sensitive potassium current conductance
L-type calcium channel mode transition parameter
calcium off-rate for troponin high affinity sites
concentration of calcium-bound subspace ATP
activation time constant of slow potassium current
sodium half-saturation constant for sodium-calcium exchange
calcium flux from network sarcoplasmic reticulum to junctional sarcoplasmic reticulum
modified sarcolemmal calcium pump current
concentration of intracellular potassium
maximum background sodium current conductance
reverse half-saturation constant for calcium ATPase
calcium on-rate for troponin high affinity sites
concentration of calcium-bound subspace ADP
total concentration of troponin low-affinity sites
rapid-activating delayed rectifier potassium current
activation potential of rapid potassium current
scale factor of sodium-calcium exchanger
ryanodine receptor PO1 - PC2 rate constant
activation potential of plateau potassium current
steady-state function of time-independent potassium current activation variable
maximum slow potassium current conductance
volume of network sarcoplasmic reticulum
calcium half-saturation constant for sodium-calcium exchange
potassium current through L-type calcium channel
concentration of calcium-bound troponin high-affinity sites
steady state function of slow potassium current activation variable
calcium half-saturation constant for time-independent potassium current
total concentration of troponin high-affinity sites
steady state function of rapid potassium current activation variable
transient outward potassium current inactivation variable
concentration of magnesium-bound subspace ADP
concentration of calcium in junctional sarcoplasmic reticulum
fraction of ryanodine receptor channels in state PO2
ryanodine receptor calcium cooperativity parameter PC1 - PO1
forward half-saturation constant for calcium ATPase
concentration of calcium-bound myoplasmic ADP
ryanodine receptor calcium cooperativity parameter PO1 - PO2
calcium flux to low-affinity troponin sites
fraction of ryanodine receptor channels in state PO1
concentration of magnesium-bound subspace ATP
calcium-bound ADP flux from subspace to myoplasm
total concentration of myoplasmic calmodulin
calcium-bound ATP flux from subspace to myoplasm
concentration of calcium-bound myoplasmic ATP
free magnesium flux from subspace to myoplasm
maximum rapid potassium current conductance
transfer time constant from network sarcoplasmic reticulum to junctional sarcoplasmic reticulum
reverse cooperativity constant for SERCA pump
slow-activating delayed rectifier potassium current
time constant for transfer of magnesium-bound ATP from subspace to myoplasm
time constant for transfer of magnesium-bound ADP from subspace to myoplasm
free calcium flux from subspace to myoplasm
ryanodine receptor PC2 - PO1 rate constant
transient outward potassium current activation variable
maximum ryanodine receptor channel calcium flux
time constant for transfer of free magnesium from subspace to myoplasm
concentration of free myoplasmic magnesium
activation curve of reverse rapid potassium current
activation time constant of rapid potassium current
volume of junctional sarcoplasmic reticulum
ryanodine receptor PO1 - PO2 rate constant
fraction of ryanodine receptor channels in state PC2
fraction of ryanodine receptor channels in state PC1
maximum background calcium current conductance
sodium current slow inactivation variable
calcium flux to high-affinity troponin sites
<documentation xmlns="http://cellml.org/tmp-documentation"> <articleinfo> Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP, ADP, and Mg2+ <author> <firstname>Catherine</firstname> <surname>Lloyd</surname> <affiliation> <shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil> </affiliation> </author> </articleinfo> Model Status This CellML model runs in both COR and OpenCell to recreate the published results. The units have been checked and they are consistent. We thank the original model author Anushka Michailova for providing us with the MATLAB code for the 2001 model on which this 2005 model is based. Please note when running a simultaion the step size has to be smaller than 0.005 seconds. <sect1 id="sec_structure"> Model Structure ABSTRACT: Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates affect cardiac excitability and contractility. To investigate how modulation by Mg(2+), ATP, and ADP of K(ATP) and L-type Ca(2+) channels influences excitation-contraction coupling, we incorporated equations for intracellular ATP and MgADP regulation of the K(ATP) current and MgATP regulation of the L-type Ca(2+) current in an ionic-metabolic model of the canine ventricular myocyte. The new model: 1), quantitatively reproduces a dose-response relationship for the effects of changes in ATP on K(ATP) current, 2), simulates effects of ADP in modulating ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+) current during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio with normal total Mg(2+) or increased free Mg(2+) with normal ATP and ADP activate K(ATP) current, shorten action potential, and alter ionic currents and intracellular Ca(2+) signals. The model predictions are in agreement with experimental data measured under normal and a variety of pathological conditions. <informalfigure float="0" id="katp_channel_diagram"> <mediaobject> <imageobject> <imagedata fileref="michailova_2005_katp.png" /> </imageobject> </mediaobject> Schematic representation of Kir6.2 and SUR2A subunit stoichiometry in cardiac octameric KATP channel. It is assumed that the single ATP molecule is sufficient to close the channel and that the binding of 2MgADP molecules to one SUR2A subunit increases the channel open probability. </informalfigure> <informalfigure float="0" id="cell_diagram"> <mediaobject> <imageobject> <imagedata fileref="michailova_2005_fullcell.png" /> </imageobject> </mediaobject> Schematic diagram of the full cell model illustrating Ca2+ and Mg2+ buffering and transport by ATP and ADP, adenine nucleotides regulation of ionic channels and pumps, and electrophysiology in a ventricular myocyte. </informalfigure> The original paper reference is cited below: Modeling Regulation of Cardiac KATP and L-type Ca2+ Currents by ATP, ADP, and Mg2+, Anushka Michailova, Jeffrey Saucerman, Mary Ellen Belik, and Andrew D. McCulloch, 2005, Biophysical Journal . PubMed ID: 18339738 </sect1> </documentation>
voltage dependence factor of sodium-calcium exchange
maximum transient outward potassium current conductance
steady state function of L-type calcium current activation variable
calcium half-saturation constant for calsequestrin
maximum plateau potassium channel conductance
concentration of calcium-bound troponin low-affinity sites
transfer time constant from subspace to myoplasm
calcium off-rate for troponin low affinity sites
sodium half-saturation constant for sodium-potassium pump
calcium half-saturation constant for EGTA
forward cooperativity constant for SERCA pump
calcium on-rate for troponin low affinity sites
potassium half-saturation constant for sodium-potassium pump
slow potassium current activation variable
activation time constant of L-type calcium current
calcium half-saturation constant for ATP
calcium half-saturation constant for magnesium-bound ADP
ryanodine receptor PO2 - PO1 rate constant
ATP-sensitive potassium current conductance
fast sodium current M-gate reversal potential
concentration of free subspace magnesium
activation curve of forward rapid potassium current
calcium half-saturation constant for calmodulin
half-saturation constant for sarcolemmal calcium pump
slow delayed rectifier current reversal potential