Critical role of ATP-induced ATP release for Ca2+ signaling in nonsensory cell networks of the developing cochlea
2016-11-15
发表期刊PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (IF:9.4[JCR-2023],10.8[5-Year])
ISSN0027-8424
卷号113期号:46页码:E7194-E7201
发表状态已发表
DOI10.1073/pnas.1616061113
摘要Spatially and temporally coordinated variations of the cytosolic free calcium concentration ([Ca2+](c)) play a crucial role in a variety of tissues. In the developing sensory epithelium of the mammalian cochlea, elevation of extracellular adenosine trisphosphate concentration ([ATP](e)) triggers [Ca2+](c) oscillations and propagation of intercellular inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ waves. What remains uncertain is the relative contribution of gap junction channels and connexin hemichannels to these fundamental mechanisms, defects in which impair hearing acquisition. Another related open question is whether [Ca2+](c) oscillations require oscillations of the cytosolic IP3 concentration ([IP3](c)) in this system. To address these issues, we performed Ca2+ imaging experiments in the lesser epithelial ridge of the mouse cochlea around postnatal day 5 and constructed a computational model in quantitative adherence to experimental data. Our results indicate that [Ca2+](c) oscillations are governed by Hopf-type bifurcations within the experimental range of [ATP](e) and do not require [IP3](c) oscillations. The model replicates accurately the spatial extent and propagation speed of intercellular Ca2+ waves and predicts that ATP-induced ATP release is the primary mechanism underlying intercellular propagation of Ca2+ signals. The model also uncovers a discontinuous transition from propagating regimes (intercellular Ca2+ wave speed > 11 mu m.s(-1)) to propagation failure (speed = 0), which occurs upon lowering the maximal ATP release rate below a minimal threshold value. The approach presented here overcomes major limitations due to lack of specific connexin channel inhibitors and can be extended to other coupled cellular systems.
关键词inositol trisphosphate calcium waves calcium oscillations cochlear nonsensory cells connexins
收录类别SCI
语种英语
资助项目University of Padua[CPDR132235]
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000388970100009
出版者NATL ACAD SCIENCES
WOS关键词GAP-JUNCTION CHANNELS ; INOSITOL 1,4,5-TRISPHOSPHATE DYNAMICS ; INNER-EAR ; CALCIUM OSCILLATIONS ; CONNEXIN 30 ; ENDOPLASMIC-RETICULUM ; ENDOTHELIAL-CELLS ; HEARING-LOSS ; GUINEA-PIG ; HEMICHANNELS
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1639
专题免疫化学研究所_特聘教授组_功能筛选实验室
通讯作者Pozzan, Tullio; Mammano, Fabio
作者单位
1.Italian Natl Res Council, Inst Cell Biol & Neurobiol, Dept Biomed Sci, I-00015 Monterotondo, RM, Italy
2.Univ Padua, Dept Phys & Astron, I-35131 Padua, Italy
3.Fdn Adv Biomed Res, Venetian Inst Mol Med, Connexin Struct & Funct Unit, I-35129 Padua, Italy
4.Italian Natl Res Council, Inst Neurosci, Dept Biomed Sci, Padua Sect, I-35129 Padua, Italy
5.Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy
6.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Lab Phenotyp Screening, Shanghai 201210, Peoples R China
通讯作者单位免疫化学研究所
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Ceriani, Federico,Pozzan, Tullio,Mammano, Fabio. Critical role of ATP-induced ATP release for Ca2+ signaling in nonsensory cell networks of the developing cochlea[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2016,113(46):E7194-E7201.
APA Ceriani, Federico,Pozzan, Tullio,&Mammano, Fabio.(2016).Critical role of ATP-induced ATP release for Ca2+ signaling in nonsensory cell networks of the developing cochlea.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,113(46),E7194-E7201.
MLA Ceriani, Federico,et al."Critical role of ATP-induced ATP release for Ca2+ signaling in nonsensory cell networks of the developing cochlea".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113.46(2016):E7194-E7201.
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