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J. Biol. Chem., Vol. 280, Issue 13, 12790-12798, April 1, 2005

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A Novel Potassium Channel in Lymphocyte Mitochondria^*

Ildikò Szabò, Jurgen Bock¶||, Andreas Jekle**, Matthias Soddemann¶, Constantin Adams¶, Florian Lang**, Mario Zoratti, and Erich Gulbins¶

From the Department of Biology and CNR Institute of Neuroscience and Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy, the ^¶Department of Molecular Biology, University of Essen, Hufelandstrasse 55, 45122 Essen, and the ^**Department of Physiology, University of Tuebingen, Gmelinstrasse 5, 72076 Tuebingen, Germany

The margatoxin-sensitive Kv1.3 is the major potassium channel in the plasma membrane of T lymphocytes. Electron microscopy, patch clamp, and immunological studies identified the potassium channel Kv1.3, thought to be localized exclusively in the cell membrane, in the inner mitochondrial membrane of T lymphocytes. Patch clamp of mitoplasts and mitochondrial membrane potential measurements disclose the functional expression of a mitochondrial margatoxin-sensitive potassium channel. To identify unambiguously the mitochondrial localization of Kv1.3, we employed a genetic model and stably transfected CTLL-2 cells, which are genetically deficient for this channel, with Kv1.3. Mitochondria isolated from Kv1.3-reconstituted CTLL-2 expressed the channel protein and displayed an activity, which was identical to that observed in Jurkat mitochondria, whereas mitochondria of mock-transfected cells lacked a channel with the characteristics of Kv1.3. Our data provide the first molecular identification of a mitochondrial potassium conductance.

Received for publication, December 2, 2004 , and in revised form, December 22, 2004.

^* This work was supported in part by an Association International Cancer Research grant, Deutsche Forschungsgemeinschaft Grant Gu 335/13-1/2, (to E. G.), an Italian Association for Cancer Research grant (to M. Z.), a long term European Molecular Biology Organization fellowship, European Molecular Biology Organization Young Investigator Program, and a Consiglio Nazionale delle Ricerche grant (to I. S.). 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.

^|| Present address: Dept. of Internal Medicine, University of Regensburg, 93053 Regensburg, Germany.

To whom correspondence may be addressed: Dept. of Biology, University of Padova, Italy, Viale G. Colombo 3, 35121 Padova, Italy. Tel.: 39-049-8276324; Fax: 39-049-8276300; E-mail: ildi{at}civ.bio.unipd.it. To whom correspondence may be addressed: Dept. of Molecular Biology, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany. Tel.: 49-201-723-3118; Fax: 49-201-723-5974; E-mail: erich.gulbins{at}uni-essen.de.

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