Modeling Ca super(2) super(+) signaling differentiation during oocyte maturation

• Published in: Cell calcium (Edinburgh) 2007-12, Vol.42 (6), p.556-564
• Main Authors: Ullah, G, Jung, P, Machaca, K
• Format: Article
• Language: English
• ISSN: 0143-4160
• DOI: 10.1016/j.ceca.2007.01.010

Ca super(2) super(+) is a fundamental intracellular signal that mediates a variety of disparate physiological functions often in the same cell. Ca super(2) super(+) signals span a wide range of spatial and temporal scales, which endow them with the specificity required to induce defined cellular functions. Furthermore, Ca super(2) super(+) signaling is highly plastic as it is modulated dynamically during normal physiological development and under pathological conditions. However, the molecular mechanisms underlying Ca super(2) super(+) signaling differentiation during cellular development remain poorly understood. Oocyte maturation in preparation for fertilization provides an exceptionally well-suited model to elucidate Ca super(2) super(+) signaling regulation during cellular development. This is because a Ca super(2) super(+) signal with specialized spatial and temporal dynamics is universally essential for egg activation at fertilization. Here we use mathematical modeling to define the critical determinants of Ca super(2) super(+) signaling differentiation during oocyte maturation. We show that increasing IP sub(3) receptor (IP sub(3)R) affinity replicates both elementary and global Ca super(2) super(+) dynamics observed experimentally following oocyte maturation. Furthermore, our model reveals that because of the Ca super(2) super(+) dependency of both SERCA and the IP sub(3)R, increased IP sub(3)R affinity shifts the system's equilibrium to a new steady state of high cytosolic Ca super(2) super(+), which is essential for fertilization. Therefore our model provides unique insights into how relatively small alterations of the basic molecular mechanisms of Ca super(2) super(+) signaling components can lead to dramatic alterations in the spatio-temporal properties of Ca super(2) super(+) dynamics.