Spread of Ca2+ in the sarcomere during fast and slow activation of mammalian cardiac myocytes

A multi-compartment model was used to estimate Ca2+ gradients in a sarcomer e of a cardiac myocyte. The mathematical model assumed Ca2+ release from th e sarcoplasmic reticulum as a driving function, and calculated Ca2+ binding to myoplasmic buffers, Ca2+ uptake by the sarcoplasmic reticulum, and diff usion of Ca2+ (and the buffers). During the fast Ca2+ transient similar to those observed during a twitch, the model predicted a large Ca2+ gradient i n the sarcomere. A trajectory of the instantaneous relation between spatial ly averaged concentrations of Ca2+ and the Ca2+-troponin complex showed a c ounterclockwise loop, indicating non-equilibrium Ca2+ binding to troponin. During slow changes in [Ca2+] with time to peaks of similar to 500 ms or lo nger, the gradient of [Ca2+] was largely dissipated and the apparent equili brium of the Ca2+-troponin binding reaction was suggested with little hyste resis of the trajectory. We conclude that a steady-state relation between [ Ca2+] and mechanical activity can be achieved uniformly in the sarcomere by slowing the rate of Ca2+ release from the sarcoplasmic reticulum.