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Originally published In Press as doi:10.1074/jbc.M405985200 on August 13, 2004

J. Biol. Chem., Vol. 279, Issue 42, 44065-44073, October 15, 2004
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Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes*

Hiroshi Hibino{ddagger}, Akikazu Fujita§, Kaori Iwai{ddagger}, Mitsuhiko Yamada{ddagger}, and Yoshihisa Kurachi{ddagger}

From the {ddagger}Department of Pharmacology II, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan and §Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan

The inwardly rectifying K+ channel subunit Kir5.1 is expressed abundantly in the brain, but its precise distribution and function are still largely unknown. Because Kir5.1 is co-expressed with Kir4.1 in retinal glial Müller cells, we have compared the biochemical and immunological properties of Kir5.1 and Kir4.1 in the mouse brain. Immunoprecipitation experiments suggested that brain expressed at least two subsets of Kir channels, heteromeric Kir4.1/5.1 and homomeric Kir4.1. Immunolabeling using specific antibodies showed that channels comprising Kir4.1 and Kir5.1 subunits were assembled in a region-specific fashion. Heteromeric Kir4.1/5.1 was identified in the neocortex and in the glomeruli of the olfactory bulb. Homomeric Kir4.1 was confined to the hippocampus and the thalamus. Homomeric Kir5.1 was not identified. Kir4.1/5.1 and Kir4.1 expression appeared to occur only in astrocytes, specifically in the membrane domains facing the pia mater and blood vessels or in the processes surrounding synapses. Both Kir4.1/5.1 and Kir4.1 could be associated with PDZ domain-containing syntrophins, which might be involved in the subcellular targeting of these astrocyte Kir channels. Because heteromeric Kir4.1/5.1 and homomeric Kir4.1 have distinct ion channel properties (Tanemoto, M., Kittaka, N., Inanobe, A., and Kurachi, Y. (2000) J. Physiol. (Lond.) 525, 587-592 and Tucker, S. J., Imbrici, P., Salvatore, L., D'Adamo, M. C., and Pessia, M. (2000) J. Biol. Chem. 275, 16404-16407), it is plausible that these channels play differential physiological roles in the K+-buffering action of brain astrocytes in a region-specific manner.


Received for publication, May 28, 2004 , and in revised form, August 6, 2004.

* This work was supported by Grant-in-aid for Specific Research on Priority Area (2) 12144207 (to Y. K.), Grant-in-aid for Young Scientists 15790134 (to H. H.), and Japan-France Integrated Action Program (SAKURA) (to Y. K.) from the Ministry of Education, Science, Sports, and Culture of Japan, by Uehara Memorial Foundation (to Y. K.), by Kanae Foundation for Life and Socio-Medical Science (to H. H.), and by Inamori Foundation (to H. H.). 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.

To whom correspondence should be addressed. Tel.: 81-6-6879-3512; Fax: 81-6-6879-3519; E-mail: ykurachi{at}pharma2.med.osaka-u.ac.jp.


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