Document Detail

Temporal switching and cell-to-cell variability in Ca2+ release activity in mammalian cells.
MedLine Citation:
PMID:  19293827     Owner:  NLM     Status:  MEDLINE    
Genetically identical cells in a uniform external environment can exhibit different phenotypes, which are often masked by conventional measurements that average over cell populations. Although most studies on this topic have used microorganisms, differentiated mammalian cells have rarely been explored. Here, we report that only approximately 40% of clonal human embryonic kidney 293 cells respond with an intracellular Ca(2+) increase when ryanodine receptor Ca(2+) release channels in the endoplasmic reticulum are maximally activated by caffeine. On the other hand, the expression levels of ryanodine receptor showed a unimodal distribution. We showed that the difference in the caffeine sensitivity depends on a critical balance between Ca(2+) release and Ca(2+) uptake activities, which is amplified by the regenerative nature of the Ca(2+) release mechanism. Furthermore, individual cells switched between the caffeine-sensitive and caffeine-insensitive states with an average transition time of approximately 65 h, suggestive of temporal fluctuation in endogenous protein expression levels associated with caffeine response. These results suggest the significance of regenerative mechanisms that amplify protein expression noise and induce cell-to-cell phenotypic variation in mammalian cells.
Naotoshi Nakamura; Toshiko Yamazawa; Yohei Okubo; Masamitsu Iino
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-17
Journal Detail:
Title:  Molecular systems biology     Volume:  5     ISSN:  1744-4292     ISO Abbreviation:  Mol. Syst. Biol.     Publication Date:  2009  
Date Detail:
Created Date:  2009-03-18     Completed Date:  2009-07-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  101235389     Medline TA:  Mol Syst Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  247     Citation Subset:  IM    
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
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MeSH Terms
Caffeine / pharmacology
Calcium / metabolism*
Cell Cycle / drug effects
Cell Line
Cell Shape / drug effects
Fluorescent Antibody Technique
Intracellular Space / drug effects,  metabolism
Models, Biological
Receptors, Purinergic / metabolism
Reproducibility of Results
Ryanodine Receptor Calcium Release Channel / metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
Time Factors
Reg. No./Substance:
0/Receptors, Purinergic; 0/Ryanodine Receptor Calcium Release Channel; 58-08-2/Caffeine; 7440-70-2/Calcium; EC Reticulum Calcium-Transporting ATPases

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