Analytical calculation of intracellular calcium wave characteristics

Abstract

We present a theoretical analysis of intracellular calcium waves propagated by calcium feedback at the inositol 1,4,5-trisphosphate (IP3) receptor. The model includes essential features of calcium excitability, but is still analytically tractable. Formulas are derived for the wave speed, amplitude, and width. The calculations take into account cytoplasmic Ca buffering, the punctate nature of the Ca release channels, channel inactivation, and Ca pumping. For relatively fast buffers, the wave speed is well approximated by V(infinity) = (J(eff)D(eff)/C0)1/2, where J(eff) is an effective, buffered source strength; D(eff) is the effective, buffered diffusion constant of Ca; and C(0) is the Ca threshold for channel activation. It is found that the saturability and finite on-rate of buffers must be taken into account to accurately derive the wave speed and front width. The time scale governing Ca wave propagation is T(r), the time for Ca release to reach threshold to activate further release. Because IP3 receptor inactivation is slow on this time scale, channel inactivation does not affect the wave speed. However, inactivation competes with Ca removal to limit wave height and front length, and for biological parameter ranges, it is inactivation that determines these parameters. Channel discreteness introduces only small corrections to wave speed relative to a model in which Ca is released uniformly from the surface of the stores. These calculations successfully predict experimental results from basic channel and cell parameters and explain the slowing of waves by exogenous buffers.