Intercellular Ca2+ wave propagation through gap-junctional Ca2+ diffusion:A theoretical study

Intercellular regenerative calcium waves in systems such as the liver and t he blowfly salivary gland have been hypothesized to spread through calcium- induced calcium release (CICR) and gap-junctional calcium diffusion. A simp le mathematical model of this mechanism is developed. It includes CICR and calcium removal from the cytoplasm, cytoplasmic and gap-junctional calcium diffusion, and calcium buffering. For a piecewise linear approximation of t he calcium kinetics, expressions in terms of the cellular parameters are de rived for 1) the condition for the propagation of intercellular waves, and 2) the characteristic time of the delay of a wave encountered at the gap ju nctions. Intercellular propagation relies on the local excitation of CICR i n the perijunctional space by gap-junctional calcium influx. This mechanism is compatible with low effective calcium diffusivity, and necessitates tha t CICR can be excited in every cell along the path of a wave. The gap-junct ional calcium permeability required for intercellular waves in the model fa lls in the range of reported gap-junctional permeability values. The concen tration of diffusive cytoplasmic calcium buffers and the maximal rate of CI CR, in the case of inositol 1,4,5-trisphosphate (IP3) receptor calcium rele ase channels set by the IP3 concentration, are shown to be further determin ants of wave behavior.