ON THE ROLES OF CA2-RETICULUM IN IP3-INDUCED CA2+ WAVES( DIFFUSION, CA2+ BUFFERS, AND THE ENDOPLASMIC)

We have investigated the effects of Ca2+ diffusion, mobile and station ary Ca2+ buffers in the cytosol, and Ca2+ handling by the endoplasmic reticulum on inositol 1,4,5-trisphosphate-induced Ca2+ wave propagatio n. Rapid equilibration of free and bound Ca2+ is used to describe Ca2 sequestration by buffers in both the cytosol and endoplasmic reticulu m (ER) lumen. Cytosolic Ca2+ regulation is based on a kinetic model of the inositol 1,4,5-trisphosphate (IP3) receptor of De Young and Keize r that includes activation and inhibition of the IP3 receptor Ca2+ cha nnel in the ER membrane and SERCA Ca2+ pumps in the ER. Diffusion of C a2+ in the cytosol and the ER and the breakdown and diffusion of IP3 a re also included in our calculations. Although Ca2+ diffusion is sever ely limited because of buffering, when conditions are chosen just belo w the threshold for Ca2+ oscillations, a pulse of IP3 or Ca2+ results in a solitary trigger wave that requires diffusion of Ca2+ for its pro pagation. In the oscillatory regime repetitive wave trains are observe d, but for this type of wave neither the wave shape nor the speed is s trongly dependent on the diffusion of Ca2+. Local phase differences le ad to waves that are predominately kinematic in nature, so that the wa ve speed (c) is related to the wavelength (lambda) and the period of t he oscillations (tau) approximately by the formula c = lambda/tau. The period is determined by features that control the oscillations, inclu ding [IP3] and pump activity, which are related to recent experiments. Both solitary waves and wave trains are accompanied by a Ca2+ depleti on wave in the ER lumen, similar to that observed in cortical preparat ions from sea urchin eggs. We explore the effect of endogenous and exo genous Ca2+ buffers on wave speed and wave shape, which can be explain ed in terms of three distinct effects of buffering, and show that exog enous buffers or Ca2+ dyes can have considerable influence on the ampl itude and width of the waves.