Modeling myocyte shortening and force generation in normal and inotropic states.
Jorge A. Negroni and José L. Puglisi
Universidad Favaloro Argentina and Loyola University Chicago
The main goal of the cardiac cell is to produce force to pump blood. Most of the available cardiac computer models reproduce action potentials, ionic currents and calcium transients. They do not, however, reproduce force generation. In order to fill this gap, we improved our mathematical model of the cardiac cell (LabHEART) with a four state diagram that incorporates the interactions between myofilaments and Ca transients with the resulting production of force. This allows the integration of the main events in Excitation-Contraction Coupling namely: action potential, Ca transients and force.
B-adrenergic stimulation is the physiological means by which the inotropic, lusitropic and chronotropic states of the heart are controlled via sympathetic stimulation. Isoproterenol, a B-adrenergic agonist, can produce an increased Ca influx through L-type channels, an increased SR Ca pump activity, and a decreased myofilament Ca sensitivity. Then, taking into account updated biblografic data we developed the B-adrenergic effects of Isoproterenol by increasing L-type Ca conductance by 100%, increasing IKs conductance by 150%, augmenting the SR Ca pump activity by 75% and decreasing the myofilament Ca sensitivity by 50%. Also, the voltage dependent activation for the L-type Ca channel and IKs were shifted to the left by 10 mV and 30 mV, respectively. The program successfully reproduces the typical reduction in AP duration as well as the increased Ca transient and developed force. This new version of LabHEART is a powerful tool for studying strategic sites of cardiac inotropy and for teaching cardiac regulation. Furthermore, this model runs on a PC, which facilitates user accessibility.