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J. Biol. Chem., Vol. 278, Issue 41, 39443-39451, October 10, 2003

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Compensatory Anion Currents in Kv1.3 Channel-deficient Thymocytes^*

From the ^aSection of Immunobiology, ^hDepartment of Pharmacology and ^jHoward Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520, the ^bRIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan, and the ^dDivision of Cellular and Molecular Biology, Toronto Western Research Institute and the ^eDepartment of Physiology, University of Toronto, Toronto, Ontario M5T 2S8, Canada

Kv1.3 is a voltage-gated potassium channel with roles in human T cell activation/proliferation, cell-mediated cytotoxicity, and volume regulation and is thus a target for therapeutic control of T cell responses. Kv1.3 is also present in some mouse thymocyte subsets and splenocytes, but its role in the mouse is less well understood. We report the generation and characterization of Kv1.3-deficient (Kv1.3^–/–) mice. In contrast to wild-type cells, the majority of Kv1.3^–/– thymocytes had no detectable voltage-dependent potassium current, although RNA and protein for several potassium channel subunits were found in the thymocyte population. Surprisingly, the level of chloride current in the Kv1.3^–/– thymocytes was increased approximately 50-fold over that in wild-type cells. There were no abnormalities in lymphocyte types or absolute numbers in thymus, spleen, and lymph nodes and no obvious defect in thymocyte apoptosis or T cell proliferation in the Kv1.3^–/– animals. The compensatory effects of the enhanced chloride current may account for the apparent lack of immune system defects in Kv1.3^–/–mice.

Received for publication, May 9, 2003 , and in revised form, July 21, 2003.

^* This work was supported in part by grants from the Natural Sciences and Engineering Research Council (NSERC) (to L. C. S.), the Canadian Institutes for Health Research (Grant MT-13657), the National Institutes of Health (Grant DC-01919) (to L. K. K.), and the Howard Hughes Medical Institute (to R. A. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^c Supported by an American Diabetes Association Mentor-Based Post-Doctoral Fellowship. Present address: Institute of Molecular Medicine & Genetics and Dept. of Medicine, Medical College of Georgia, 1120 15th St., Augusta, GA 30912.

^f Supported by an Ontario Graduate Scholarship and a Santalo Scholarship (University of Toronto).

^g Supported by an NSERC Scholarship.

ⁱ To whom correspondence may be addressed. Tel.: 416 603-5800 (ext. 2052); Fax: 416 603-5745; E-mail: schlicht{at}uhnres.utoronto.ca.

^k An Investigator of the Howard Hughes Medical Institute. To whom correspondence may be addressed. Tel.: 203-737-2216; Fax: 203-737-2958; E-mail: richard.flavell{at}yale.edu.

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