T-Type voltage-sensitive calcium channels mediate mechanically-induced intracellular calcium oscillations in osteocytes by regulating endoplasmic reticulum calcium dynamics.

Autor: Brown GN; Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA., Leong PL; Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA., Guo XE; Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA. Electronic address: ed.guo@columbia.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2016 Jul; Vol. 88, pp. 56-63. Date of Electronic Publication: 2016 Apr 21.
DOI: 10.1016/j.bone.2016.04.018
Abstrakt: One of the earliest responses of bone cells to mechanical stimuli is a rise in intracellular calcium (Ca(2+)), and osteocytes in particular exhibit robust oscillations in Ca(2+) when subjected to loading. Previous studies implicate roles for both the endoplasmic reticulum (ER) and T-Type voltage-sensitive calcium channels (VSCC) in these responses, but their interactions or relative contributions have not been studied. By observing Ca(2+) dynamics in the cytosol (Ca(2+)cyt) and the ER (Ca(2+)ER), the focus of this study was to explore the role of the ER and T-Type channels in Ca(2+) signaling in bone cells. We demonstrate that inhibition of T-Type VSCC in osteocytes significantly reduces the number of Ca(2+)cyt responses and affects Ca(2+)ER depletion dynamics. Simultaneous observation of Ca(2+) exchange among these spaces revealed high synchrony between rises in Ca(2+)cyt and depressions in Ca(2+)ER, and this synchrony was significantly reduced by challenging T-Type VSCC. We further confirmed that this effect was mediated directly through the ER and not through store-operated Ca(2+) entry (SOCE) pathways. Taken together, our data suggests that T-Type VSCC facilitate the recovery of Ca(2+)ER in osteocytes to sustain mechanically-induced Ca(2+) oscillations, uncovering a new mechanism underlying the behavior of osteocytes as mechanosensors.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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