| Title: |
Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes |
| Authors: |
Ravshan Z. Sabirov; Yasunobu Okada; Ranokhon S. Kurbannazarova; Svetlana V. Bessonova |
| Source: |
International Journal of Molecular Sciences, Vol 12, Iss 12, Pp 9125-9137 (2011) |
| Publisher Information: |
MDPI AG |
| Publication Year: |
2011 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
thymocytes; volume regulation; anion channels; phloretin; DIOA; Biology (General); QH301-705.5; Chemistry; QD1-999 |
| Description: |
Channel-mediated trans-membrane chloride movement is a key process in the active cell volume regulation under osmotic stress in most cells. However, thymocytes were hypothesized to regulate their volume by activating a coupled K-Cl cotransport mechanism. Under the patch-clamp, we found that osmotic swelling activates two types of macroscopic anion conductance with different voltage-dependence and pharmacology. At the single-channel level, we identified two types of events: one corresponded to the maxi-anion channel, and the other one had characteristics of the volume-sensitive outwardly rectifying (VSOR) chloride channel of intermediate conductance. A VSOR inhibitor, phloretin, significantly suppressed both macroscopic VSOR-type conductance and single-channel activity of intermediate amplitude. The maxi-anion channel activity was largely suppressed by Gd3+ ions but not by phloretin. Surprisingly, [(dihydroindenyl)oxy] alkanoic acid (DIOA), a known antagonist of K-Cl cotransporter, was found to significantly suppress the activity of the VSOR-type single-channel events with no effect on the maxi-anion channels at 10 μM. The regulatory volume decrease (RVD) phase of cellular response to hypotonicity was mildly suppressed by Gd3+ ions and was completely abolished by phloretin suggesting a major impact of the VSOR chloride channel and modulatory role of the maxi-anion channel. The inhibitory effect of DIOA was also strong, and, most likely, it occurred via blocking the VSOR Cl− channels. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
http://www.mdpi.com/1422-0067/12/12/9125/; https://doaj.org/toc/1422-0067; https://doaj.org/article/1163fc7e0f0841fc9a0c41355d5b047e |
| DOI: |
10.3390/ijms12129125 |
| Availability: |
https://doi.org/10.3390/ijms12129125; https://doaj.org/article/1163fc7e0f0841fc9a0c41355d5b047e |
| Accession Number: |
edsbas.995A4B31 |
| Database: |
BASE |