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Int. J. Mol. Sci. 2011, 12(12), 9125-9137; doi:10.3390/ijms12129125
Article

Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes

1,2,3
, 1,2
, 1,*  and 1,2,3
Received: 25 October 2011; in revised form: 10 November 2011 / Accepted: 24 November 2011 / Published: 8 December 2011
(This article belongs to the Special Issue Membrane Transport)
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Abstract: 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.
Keywords: thymocytes; volume regulation; anion channels; phloretin; DIOA thymocytes; volume regulation; anion channels; phloretin; DIOA
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Kurbannazarova, R.S.; Bessonova, S.V.; Okada, Y.; Sabirov, R.Z. Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes. Int. J. Mol. Sci. 2011, 12, 9125-9137.

AMA Style

Kurbannazarova RS, Bessonova SV, Okada Y, Sabirov RZ. Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes. International Journal of Molecular Sciences. 2011; 12(12):9125-9137.

Chicago/Turabian Style

Kurbannazarova, Ranokhon S.; Bessonova, Svetlana V.; Okada, Yasunobu; Sabirov, Ravshan Z. 2011. "Swelling-Activated Anion Channels Are Essential for Volume Regulation of Mouse Thymocytes." Int. J. Mol. Sci. 12, no. 12: 9125-9137.


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