ANALYTICAL CALCULATION OF INTRACELLULAR CALCIUM WAVE CHARACTERISTICS

We present a theoretical analysis of intracellular calcium waves propa gated by calcium feedback at the inositol 1,4,5-trisphosphate (IP3) re ceptor. The model includes essential features of calcium excitability, but is still analytically tractable. Formulas are derived for the wav e speed, amplitude, and width. The calculations take into account cyto plasmic 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)/C-0)(1/ 2), where J(eff) is an effective, buffered source strength; D-eff is t he effective, buffered diffusion constant of Ca; and C-0 is the Ca thr eshold for channel activation, It is found that the saturability and f inite on-rate of buffers must be taken into account to accurately deri ve the wave speed and front width, The time scale governing Ca wave pr opagation is T-r, the time for Ca release to reach threshold to activa te further release. Because IP3 receptor inactivation is slow on this time scale: channel inactivation does not affect the wave speed. Howev er, inactivation competes with Ca removal to limit wave height and fro nt length, and for biological parameter ranges, it is inactivation tha t determines these parameters. Channel discreteness introduces only sm all corrections to wave speed relative to a model in which Ca is relea sed uniformly from the surface of the stores. These calculations succe ssfully predict experimental results from basic channel and cell param eters and explain the slowing of waves by exogenous buffers.