Abstract

Calcium (Ca2+) signals are ubiquitous. Most intracellular Ca2+ signals involve the release of Ca2+ from the endoplasmic reticulum (ER) through Inositol 1,4,5-Trisphosphate Receptors (IP3Rs). The non-uniform spatial organization of IP3Rs and the fact that their individual openings are coupled via cytosolic Ca2+ are key factors for the variety of spatio-temporal distributions of the cytosolic [Ca2+] and the versatility of the signals. In this paper we combine experiments performed in untreated and in progesterone-treated Xenopus laevis oocytes and mathematical models to investigate how the interplay between geometry (the IP3R spatial distribution) and dynamics (the processes that characterize the release, transport, and removal of cytosolic Ca2+) affects the resulting signals. Signal propagation looks more continuous and spatially uniform in treated (mature) than in untreated (immature) oocytes. This could be due to the different underlying IP3R spatial distribution that has been observed in both cell types. The models, however, show that the rate of cytosolic Ca2+ removal, which is also different in both cell types, plays a key role affecting the coupling between Ca2+ release sites in such a way that the effect of the underlying IP3R spatial distribution can be modified.

Highlights

  • Calcium (Ca2+) signaling is involved in many physiological processes (Berridge et al, 1998)

  • Their versatility relies on the variety of spatio-temporal distributions that the intracellular Ca2+ concentration can display. These distributions are the result of the interplay between geometry and dynamics

  • We sought to determine the relative role of the non-uniform IP3R spatial distribution on the resulting signal

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Summary

INTRODUCTION

Calcium (Ca2+) signaling is involved in many physiological processes (Berridge et al, 1998). In our experiments we observe differences in the way that Ca2+ is cleared in the two cell types once the IP3 release is stopped which can be related to the existence of larger Ca2+ concentration gradients (i.e., less uniform Ca2+ distribution) in oocytes than in eggs This distinction between saltatory and continuous signals is consistent with the differences between the waves elicited in immature oocytes (Yao et al, 1995) and the fertilization wave in eggs (Fontanilla and Nuccitelli, 1998). This shows that the mode of propaga√tion (which determines whether v is proportional to D/d or to Dτ ) is key to set the wave speed There is another difference between the waves elicited experimentally in immature oocytes and the fertilization wave: while the IP3 distribution is approximately spatially uniform, within the observed region, this situation does not necessarily hold in the fertilization case. Different inhibition levels at more or less densely packed clusters were observed in the simulations of Ullah et al (2007)

Oocyte Preparation
Confocal Microscopy
Image Analysis and Event Characterization
Numerical Simulations
RESULTS
Experiments
DISCUSSION AND CONCLUSIONS
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