Ca2+ Signaling in the Near Plasma Membrane Microdomain of Non-Excitable Cells

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Title: Ca2+ Signaling in the Near Plasma Membrane Microdomain of Non-Excitable Cells
Author: Yao, Jian
Abstract: Calcium is the most versatile second messenger and plays fundamental roles in orchestrating enzyme secretion in exocrine acinar cells . Previous studies in excitable cells demonstrated the existence of high Ca2+ microdomains . The major function of such microdomains is to create high local calcium concentration to activate various calcium -dependent signaling events . However , in non -excitable cells , direct evidence of such microdomains is absent . The goal of my study is to characterize the properties of high Ca2+ microdomains in acinar cells and explore its physiological relevance in the context of the secretory functions . By combining Total Internal Reflection Fluorescence Microscopy (TIRFM ) technique and wide -field fluorescence imaging , I was able to quantify and compare changes in the concentration of free Ca2+ in the near membrane microdomains ( ?[Ca2+]PM ) and in the bulk cytosol ( ?[Ca2+]Cyto ) . ?[Ca2+]PM is about 3 -fold larger than ?[Ca2+]Cyto under maximal agonist stimulation , while resting [Ca2+]PM and [Ca2+]Cyto shows no difference . Near membrane microdomains also showed greater Ca2+ influx following store depletion induced either by activating surface receptor or by inhibiting SERCA pump . In response to physiological strength of stimulation , Ca2+ oscillation in the two compartments showed significantly different dynamics . The activation mechanisms of the Ca2+ -induced Ca2+ release (CICR ) are well established in cardiac and skeletal muscles and involves high Ca2+ microdomains . My study was the first to demonstrate the presence of CICR in the parotid acinar cell . In these cells , minimal activation of Ca2+ influx by partially depleting the stores , either by directly activating the cell surface receptor or by inhibiting SERCA , leads to an explosive release of Ca2+ from the majority of the stores , mediated presumably by RyR away from microdomains . The last part of my study is on the effects of chronic ER stress on Ca2+ signaling . The study suggests that ER stress induced by PERK mutation impeded both the efficiency and fidelity of Ca2+ signaling . My work validates the existence of near plasma membrane microdomains in non -excitable exocrine cells . The fact that [Ca2+]PM and [Ca2+]Cyto differ in many ways suggests that microdomains is the central signaling platform in these cells .
URI: http : / /hdl .handle .net /2152 .5 /864
Date: 2011-02-01

Citation

Ca2+ Signaling in the Near Plasma Membrane Microdomain of Non-Excitable Cells. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /864 .

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