Modelling Interval-Force Relations in Cardiac Muscle

In 2000, Rice, Jafri and Winslow published a detailed model of the short-term interval-force relations in cardiac muscle. This detailed model is derived from two previously published models: The Jafri-Rice-Winslow Ventricular Model, 1998 and Cooperative Mechanisms in Cardiac Muscle, Rice et al., 1999. The second model adds force generation to an electrophysiological model. These models are linked via a calcium transient provided by the cardiac cell model. This calcium transient is the stimulus for Ca²⁺ binding to troponin, and subsequent force generation by the myofilaments.

This example is naturally illustrated by use of the import and reuse features of CellML 1.1. Components and units are imported from the Jafri et al. 1998 model into the Rice et al. 2000 model. The components of the chemomechanical model are built in the current, importing model. These are then connected up to the relevant imported components.

In their second modelling approach, J. Jeremy Rice, M. Saleet Jafri and Raimond L. Winslow develop a more detailed ventricular cell model that is able to simulate action potentials, Ca²⁺-handling mechanisms, and isometric force generation by the myofilaments. This single comprehensive (or maximal) model combines two previously developed models (see The Jafri-Rice-Winslow Ventricular Model, 1998 and Cooperative Mechanisms in Cardiac Muscle, Rice et al., 1999). The first ventricular cell model describes membrane currents and Ca²⁺-handling, and the second model of myofilaments provides the force generation of muscle contraction (see Figure 1 below). The ventricular cell model provides the Ca²⁺ needed to drive the myofilament contraction. This is a feedforward pathway in which Ca²⁺ binds to troponin and initiates force generation by triggering myofilament contraction. A feedback pathway also links the two models, as the affinity of troponin for Ca²⁺ is a function of developed force.

Figure 1. Schematic diagram of a detailed, single ventricular cell model which is able to simulate action potentials, Ca²⁺-handling and isometric force generation by myofilaments.

Simulation results generated from the model support experimental data. They suggest that short-term interval-force relations result mainly from the interplay between ryanodine receptor adaptation and SR Ca²⁺ loading with additional contributions from membrane currents and myofilament activation.

Modeling short-term interval-force relations in cardiac muscle J. Jeremy Rice, M. Saleet Jafri and Raimond L. Winslow, 2000, American Journal of Physiology, 278, H913-H931. (Full text and PDF versions of the article are available for Journal Members on the American Journal of Physiology website.)