Cardiac Atrial Cell (Courtemanche et al 1998)

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Accession:3800
Marc Courtemanche, Rafael J. Ramirez, and Stanley Nattel. Ionic mechanisms underlying human atrial action potential properties insights from a mathematical model Am J Physiol Heart Circ Physiol 1998 275: H301-H321. The implementation of this model in NEURON was contributed by Ingemar Jacobson.
Reference:
1 . Courtemanche M, Ramirez RJ, Nattel S (1998) Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model. Am J Physiol 275:H301-21 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Cardiac atrial cell; Heart cell;
Channel(s): I Na,t; I L high threshold; I K; I Sodium; I Calcium; I Potassium;
Gap Junctions:
Receptor(s):
Gene(s): Kv4.3 KCND3; Kv1.5 KCNA5; HERG KCNH2;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Ion Channel Kinetics; Action Potentials; Heart disease; Calcium dynamics;
Implementer(s): Jacobson, Ingemar [Ingemar.Jacobson at astrazeneca.com];
Search NeuronDB for information about:  I Na,t; I L high threshold; I K; I Sodium; I Calcium; I Potassium;
Version 2002-08-30 Temperature sensitivity changed:(Behavior unchanged at 27 C)

Ingemar Jacobson contributed this model with the comment
"...  Following
compilation the model can be launched from the startatrial1.hoc file -
you then just need to start the simulation - I suggest with the
variable time step ticked. I had some problems with the intracellular
Ca2+-dynamics and for = clarity I had to split it into several files -
now it works reasonably well also for CVODE.  Having defined the model
files of the various cardiac currents it is an easy task to convert
the atrial model to more or less any other cardiac cell type. 
Hopefully this will be of some use for cardiac electrophysiogists. 
..."
and also
"...
 Perhaps some of the model files can serve as templates for neuronal
channels- the molecular correlate for the cardiac Ito is Kv4.3, for IKur
it is Kv1.5; for IKr - it is HERG, all these being potassium channels
you will find in the CNS.
 ..."

Questions about the model should be directed to the original authors.
Questions about the computer implementation should be directed to
Dr. Jacobson. Questions about the database presentation should be
directed to Michael Hines. Following is a slightly expanded copy of
the "about" screen that pops up when the model is executed.
Running the model via the mosinit.hoc file (executed automatically by the
autolaunch process) will generate the heart action potential
shown in the ap.gif file.

-------------

The Virtual Human Atrial Cell is assembled for NEURON  by
	Ingemar Jacobson
	AstraZeneca R & D, Mölndal Sweden 
	emailaddress ingemar.jacobson@astrazeneca.com

The model is based on the paper by

Marc Courtemanche, Rafael J. Ramirez, and Stanley Nattel.
Ionic mechanisms underlying human atrial action potential properties
insights from a mathematical model 
Am J Physiol Heart Circ Physiol 1998 275: H301-H321.

and conductance values are adjusted to give appropriate current
densities.  Pumps, exchangers and an additional electroneutral ion
accumulation mechanism are sat so that ion concentrations are stable at
a pacing rate of 1 Hz. 

The kinetics of IKur is modified to fit data of
 Feng et al Am J Physiol 1998 275(Heart Circ Physiol 44):H1717-H1725.

The possibility to include a nonspecific cation-current with kinetics
similar to IKur is also given in the IKur mechanism For the
intracellular Ca dynamics to work the mechanisms Cadynam, ca_jsr,
Ca_jsracc and ca_nsracc have to be inserted.  For simulation of
intracellular Na+-ion and K+-ion changes the mechanisms Na_acc and K_acc
have to be inserted.  The model is free to use provided acknowledgement
is given to the developers of NEURON

nseg = 1
L=100 um
diam=16 um
cm = 2 uF/cm^2
Vi - intracellular volume 13668um^3

SR -sarcoplasmatic reticulum, 
JSR - junctional SR - SR release compartment
Vrel - SR release compartment volume  96.48um^3
cri - calcium ion conc. in JSR
icr - calcium release current from JSR
krel - Max. release rate for icr 30mse-1

NSR - network SR - SR uptake compartment
Vup - SR uptake compartment volume  1109.52um^3
cui - calcium ion conc. in NSR
cupmax - Max. Ca2+ conc. in uptake compartment 15mM
Iupmax - Max. uptake Ca2+ current (Iup) by NSR 0.005 mM/ms
Kup - [Ca2+]i half-saturation constant for Iup 0.00092mM
Trpn - Total troponin conc. in myoplasm  0.07mM
Kmtrpn - [Ca2+]i half-saturation constant for troponin 0.0005mM
Cmdn - Total calmodulin conc. in myoplasma 0.05 mM 
Kmcmdn - [Ca2+]i half-saturation constant for calmodulin 0.00238mM
Csqn - Total calsequesterin conc. in SR release compartment 10mM
Kmcsqn - [Ca2+]JSR (cri) half-saturation constant for calsequesterin 0.8mM 
IpCamax - Max. Ca2+ pump current (IpCa) 0.00055mA/cm2
gCaL - Max ICaL conductance 0.248mS/cm2
gK1 - Max. IK1 conductance 0.1567mS/cm2
gKr - Max. IKr conductance 0.0588mS/cm2
gKs - Max. IKs conductance 0.258mS/cm2
gKur - Max. IKur conductance 0.13195mS/cm2
gnonspec - Max nonspecific Ication conductance 0 mS/cm2
gnabar - Max INa conductance 15.6 mS/cm2
gbNa - Max. Ibackground (Na) conductance 1.34e-3mS/cm2
gbCa - Max. Ibackground (Ca2+)conductance 2.26e-3mS/cm2
gto - Max. Ito conductance 0.33 mS/cm2
Kneutral - electroneutral K+ - accumulation 3e-5mA/cm2
ImaxNax - Max Ca2+/Na+ exchange current (INaCa) 3.5mA/cm2 
KnNacx - [Na+]o half-saturation constant for INaCa 87.5 mM
KcNacx - [Ca2+]o half-saturation constant for INaCa 1.38 mM
Naneutral - electroneutral Na+ - accumulation 3.5e-5 mA/cm2
INaKmax - Max. Na+/K+-pump current (INaK) 0.00219 mA/cm2
Kmnai - [Na+]i half-saturation constant for InaK 10mM
Kmko - [K+]o half-saturation constant for InaK 1.5mM
Tauct - scaling factor activation 
Tauinactf - scaling factor fast inactivation 
Tauinacts - scaling factor slow inactivation 


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