Rate Dependent Phenomena and CaMKII Pathway

Models and Simulations > Ion Channels | Cardiac Cells | Cardiac Tissue

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

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

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 (I_NaL) and Ca²⁺ dependent transient outward current (I_to2, in addition to I_to1), (3) dynamic intracellular Cl^– handling and (4) a novel formulation of calcium release from the junctional sarcoplasmic reticulum (JSR). Interaction between dihydropyridine receptors (I_CaL) and ryanodine receptors (RyR) occurs in a restricted Ca²⁺ subspace. The calcium release formulation incorporates activation of RyR by I_CaL, Ca²⁺-dependent inactivation of RyR, and modulation of RyR open-probability by both JSR and subspace Ca²⁺.

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:

SIMULATION NOTES:

• Achieving steady state during ultra-long term continuous pacing
• Modifications to HRD code for simulation of propagation
• Matlab code and C++ code
• Sample output and directions on using the code