Ceriani, F. orcid.org/0000-0002-5366-341X, Pozzan, T. and Mammano, F. (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 (PNAS) ISSN 1091-6490, 113 (46). E7194-E7201. ISSN 1091-6490
Abstract
Spatially and temporally coordinated variations of the cytosolic free calcium concentration ([Ca(2+)]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 [Ca(2+)]c oscillations and propagation of intercellular inositol 1,4,5-trisphosphate (IP3)-dependent Ca(2+) 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 [Ca(2+)]c oscillations require oscillations of the cytosolic IP3 concentration ([IP3]c) in this system. To address these issues, we performed Ca(2+) 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 [Ca(2+)]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 Ca(2+) waves and predicts that ATP-induced ATP release is the primary mechanism underlying intercellular propagation of Ca(2+) signals. The model also uncovers a discontinuous transition from propagating regimes (intercellular Ca(2+) wave speed > 11 μm⋅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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © PNAS 2016 |
Keywords: | calcium oscillations; calcium waves; cochlear nonsensory cells; connexins; inositol trisphosphate |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 07 Nov 2016 16:36 |
Last Modified: | 30 Jun 2023 15:43 |
Status: | Published |
Publisher: | National Academy of Sciences |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.1616061113 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107012 |