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 sarcomere of a cardiac myocyte. The mathematical model assumed Ca2+ release from the sarcoplasmic reticulum as a driving function, and calculated Ca2+ binding to myoplasmic buffers, Ca2+ uptake by the sarcoplasmic reticulum, and diffusion of Ca2+ (and the buffers). During the fast Ca2+ transient similar to those observed during a twitch, the model predicted a large Ca2+ gradient in the sarcomere. A trajectory of the instantaneous relation between spatially averaged concentrations of Ca2+ and the Ca2+-troponin complex showed a counterclockwise loop, indicating non-equilibrium Ca2+ binding to troponin. During slow changes in Ca2+] with time to peaks of approximately 500 ms or longer, the gradient of Ca2+] was largely dissipated and the apparent equilibrium of the Ca2+-troponin binding reaction was suggested with little hysteresis 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.