Abstract

Calcium signaling represents one of the most important signaling cascades in cells and regulates diverse processes such as exocytosis, muscle contraction and relaxation, gene expression and cell growth. G protein-coupled receptors (GPCRs) are the most important family of receptors that activate calcium signaling. Since calcium signaling regulates a large number of physiological responses, it is intriguing that how changes in cytosolic calcium levels by a wide range of stimuli lead to signal-specific physiological responses in the cellular interior. In order to address this issue, we have analyzed temporal calcium profiles induced by two GPCRs, the serotonin1A and purinergic receptors. In this work, we have described a set of parameters for the analysis of calcium transients that could provide novel insight into mechanisms responsible for maintaining signal specificity by shaping calcium transients. An interesting feature of calcium signaling that has emerged from our analysis is that the profile of individual transients in a calcium response could play an important role in maintaining downstream signal specificity. In summary, our analysis offers a novel approach to identify differences in calcium response patterns induced by various stimuli.

Highlights

  • Calcium signaling represents one of the most important signaling cascades in cells

  • Since G protein-coupled receptors (GPCRs) regulate multiple physiological processes, they have emerged as major targets for the development of novel drug candidates in all clinical areas [9]

  • We have described a set of parameters for calcium transients that could provide novel insight into mechanisms responsible for maintaining the specificity of signals by shaping calcium transients

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Summary

Introduction

Calcium signaling represents one of the most important signaling cascades in cells. The indispensability of calcium signaling is apparent from the fact that it governs a large number of processes in cells [1,2,3]. The difference in calcium concentration between the cytosol and these intracellular stores or extracellular spaces could be utilized very effectively to deliver signals across the cell membrane. This implies that any stimulus that activates calcium signaling leads to release of calcium from these stores and a subsequent increase in cytosolic calcium concentration [4]. The released calcium in the cytosol is either actively taken up by ER through calcium channels called sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), or effluxed out of the cell through calcium channels present on the plasma membrane These processes lead to the interesting occurrence of calcium spikes/transients which involves repetitive rise and decay of calcium concentration in the cytosol. These results would provide useful insights into processes involved in shaping the calcium profile in response to different ligands/stimuli

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