The Hund-Rudy Dynamic (HRd) Model of the Canine Ventricular Myocyte

The Hund-Rudy dynamic (HRd) model is based on data from the canine epicardial ventricular myocyte. Rate-dependent phenomena associated with ion channel kinetics, action potential properties and Ca2+ handling are simulated by the model. Distinguishing features of the HRd include (1) regulation of Ca2+-handling by Ca2+/calmodulin dependent protein kinase (CaMKII), (2) incorporation of the late Na+ current (INaL) and Ca2+ dependent transient outward current (Ito2, in addition to Ito1), (3) dynamic intracellular Cl- handling and (4) a novel formulation of calcium release from the junctional sarcoplasmic reticulum (JSR). Interaction between dihydropyridine receptors (ICaL) and ryanodine receptors (RyR) occurs in a restricted Ca2+ subspace. The calcium release formulation incorporates activation of RyR by ICaL, Ca2+-dependent inactivation of RyR, and modulation of RyR open-probability by both JSR and subspace Ca2+.

 

Originally published in:

                        "Rate dependence and regulation of action potential and calcium transient
                                in a canine cardiac ventricular cell model."
                                Hund TJ, Rudy Y.
                               
Circulation. 2004 Nov 16;110(20):4008-74.

ERRATUM:

In the online supplement for the HRD code, there is a typo in the formulation of the Na+ current rate constant . The equation should read:

If  mV,

           

           

 

SIMULATION NOTES :

Note on achieving steady state during ultra-long term continuous pacing.

Note on modifications to HRD code for simulation of propagation.

 

To directly access the C++ code, (Last updated on September 29, 2005) click here .

 

To download the Matlab code, (Last updated on October 5, 2005.  Backward Compatibility with Matlab 6.5) click here .

 

For sample output, and directions on how to use the code click here.

 

To view a concise description of the model formulations, click here.

 

Question about the model? Email Tom Hund. Question about the code? Email Keith Decker

 

Linked Index to the C++ Code and Descriptions of Formulations

A. Currents

Variable

Formulation

Code

 

1. fast Na+ current

ina

link

definition

implementation

2. late Na+ current

inal

link

definition

implementation

3. L-type Ca2+ current

ical

link

definition

implementation

4. rapid delayed rectifier K+ current

ikr

link

definition

implementation

5. slow delayed rectifier K+ current

iks

link

definition

implementation

6. 4AP-sensitive transient outward K+ current

ito1

link

definition

implementation

7. Ca2+ dependent transient outward Cl- current

ito2

link

definition

implementation

8. time- independent K+ current

ik1

link

definition

implementation

9. background Ca2+ current

icab

link

definition

implementation

10. plateau K+ current

ikp

link

definition

implementation

11. Cl- background current

iclb

link

definition

implementation

B. Pumps and Exchangers

 

 

 

 

1. Na+-Ca2+ exchanger

inaca

link

definition

implementation

2. Na+-K+ pump

inak

link

definition

implementation

3. Sarcolemmal Ca2+ pump

ipca

link

definition

implementation

C. Transporters

 

 

 

 

1. Na+-Cl- cotransporter

ctnacl

link

definition

implementation

2. K+-Cl- cotransporter

ctkcl

link

definition

implementation

D. Ionic Fluxes

 

 

 

 

1. Ca2+ leak from JSR to myoplasm

qleak

link

definition

implementation

2. Ca2+ release from JSR to subspace

qrelease

link

definition

implementation

3. Ca2+ transfer from NSR to JSR

qtr

link

definition

implementation

4. Ca2+ uptake from myoplasm to NSR

qup

link

definition

implementation

E. Dynamic Concentrations

 

 

 

 

1. myoplasmic Na+

nai

link

 

implementation

2. myoplasmic K+

ki

link

 

implementation

3. myoplasmic Cl-

cli

link

 

implementation

4. myoplasmic Ca2+

cai

link

 

implementation

5. JSR Ca2+

cajsr

link

 

implementation

6. NSR Ca2+

cansr

link

 

implementation

7. restricted space Ca2+

car

link

 

implementation

8. CaMKinase

camk

link

 

implementation