Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/110923
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Type: | Journal article |
Title: | Regulation of Orai1/STIM1 mediated ICRAC by intracellular pH |
Author: | Gavriliouk, D. Scrimgeour, N. Grigoryev, S. Ma, L. Zhou, F. Barritt, G. Rychkov, G. |
Citation: | Scientific Reports, 2017; 7(1):9829-1-9829-12 |
Publisher: | Springer Nature |
Issue Date: | 2017 |
ISSN: | 2045-2322 2045-2322 |
Statement of Responsibility: | D. Gavriliouk, N.R. Scrimgeour, S. Grigoryev, L. Ma, F.H. Zhou, G.J. Barritt, G.Y. Rychkov |
Abstract: | Ca²⁺ release activated Ca²⁺-(CRAC) channels composed of two cellular proteins, Ca²⁺-sensing stromal interaction molecule 1 (STIM1) and pore-forming Orai1, are the main mediators of the Ca²⁺ entry pathway activated in response to depletion of intracellular Ca²⁺ stores. Previously it has been shown that the amplitude of CRAC current (ICRAC) strongly depends on extracellular and intracellular pH. Here we investigate the intracellular pH (pHi) dependence of ICRAC mediated by Orai1 and STIM1ectopically expressed in HEK293 cells. The results indicate that pHi affects not only the amplitude of the current, but also Ca²⁺ dependent gating of CRAC channels. Intracellular acidification changes the kinetics of ICRAC, introducing prominent re-activation component in the currents recorded in response to voltage steps to strongly negative potentials. ICRAC with similar kinetics can be observed at normal pHi if the expression levels of Orai1 are increased, relative to the expression levels of STIM1. Mutations in the STIM1 inactivation domain significantly diminish the dependence of ICRAC kinetics on pHi, but have no effect on pHi dependence of ICRAC amplitude, implying that more than one mechanism is involved in CRAC channel regulation by intracellular pH. |
Keywords: | Cell Line Intracellular Space Humans Calcium Neoplasm Proteins Ion Channel Gating Gene Expression Regulation Mutation Hydrogen-Ion Concentration Stromal Interaction Molecule 1 ORAI1 Protein Calcium Release Activated Calcium Channels |
Rights: | © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
DOI: | 10.1038/s41598-017-06371-0 |
Grant ID: | http://purl.org/au-research/grants/arc/DP140100259 |
Published version: | http://dx.doi.org/10.1038/s41598-017-06371-0 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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hdl_110923.pdf | Published version | 2.2 MB | Adobe PDF | View/Open |
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