Mechanisms of length history-dependent tension in an ionic model of the cardiac myocyte

The ionic model of the ventricular myocyte developed by Luo and Rudy (Circ. Res. 74:1071-1096, 1994) was used to investigate potential mechanisms of the slow changes in stress (SCS) that follow step changes in muscle length. A step change in myofilament sensitivity alone caused an immediate increase in active tension, but no SCS. The effects of additional step changes in the parameters of sarcolemmal ion fluxes were examined for each ion flu in the model. Changes in the coefficients of Ca2+ or K+ channels did not produce SCS. SCS was produced by step changes in parameters of the Na+-K+ pump or the Na+ leak current. This simulated mechanism was mediated through a slow increase in intracellular Na+ concentration and a resulting increase in systolic Ca2+ entry through the Na+/Ca2+ exchanger. The model reproduced the effects of several experimental interventions such as sarcoplasmic reticulum Ca2+ depletion, "diastolic" length changes, and changes in extracellular Ca2+. Thus SCS in cardiac muscle may be caused by length-induced changes in sarcolemmal Na+ fluxes.