Cloning and Functional Characterization of a Novel ATP-sensitive Potassium Channel Ubiquitously Expressed in Rat Tissues, including Pancreatic Islets, Pituitary, Skeletal Muscle, and Heart (*)
- Nobuya Inagaki(1),
- Yoshiyuki Tsuura(2),
- Noriyuki Namba(1),
- Kazuhiro Masuda(2),
- Tohru Gonoi(4),
- Minoru Horie(3),
- Yutaka Seino(2),
- Masanari Mizuta(1) and
- Susumu Seino(1)(§)
- From the (1)Division of Molecular Medicine, Center for Biomedical Science, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan,
- (2)Department of Metabolism and Clinical Nutrition and
- (3)Third Department of Internal Medicine, Kyoto University School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan, and
- (4)Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan
- § To whom correspondence should be addressed. Tel.: 81-43-226-2187; Fax: 81-43-221-7803.
Abstract
ATP-sensitive K
(K
) channels play a crucial role in coupling metabolic energy to the membrane potential of cells. We have isolated a cDNA encoding
a novel member (uK
-1) of the inward rectifier K
channel family from a rat pancreatic islet cDNA library. Rat uK
-1 is a 424-amino acid residue protein (Mr = 47,960). Electrophysiological studies of uK
-1 expressed in Xenopus laevis oocytes show that uK
-1 is a weak rectifier and is blocked with Ba
ions. Single-channel patch clamp study of clonal human kidney epithelial cells (HEK293) transfected with uK
-1 cDNA reveals that uK
-1 closes in response to 1 mM ATP and has a single channel conductance of 70 ± 2 picosiemens (n = 6), indicating that uK
-1 is an ATP-sensitive inward rectifier K
channel. In addition, uK
-1 is activated by the K
channel opener, diazoxide. RNA blot analysis shows that uK
-1 mRNA is expressed ubiquitously in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart, suggesting
that uK
-1 may play a physiological role as a link between the metabolic state and membrane K
permeability of cells in almost every normal tissue. Since uK
-1 shares only 43-46% amino acid identity with members of previously reported inward rectifier K
channel subfamilies, including ROMK1, IRK1, GIRK1, and cK
-1, uK
-1 is not an isoform of these subfamilies and, therefore, represents a new subfamily of the inward rectifier K
channel family having two transmembrane segments.
Footnotes
-
↵* This research was supported by scientific research grants from the Ministry of Education, Science and Culture and from the Ministry of Health and Welfare, Japan; by a grant for diabetes research from Otsuka Pharmaceutical Co., Ltd.; by a grant from Yamanouchi Foundation for Research on Metabolic Disorders; by a grant provided by Ichiro Kanehara Foundation; and by a grant from the Juvenile Diabetes Foundation International. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(TM)/EMBL Data Bank with accession number(s) D42145[GenBank].
-
↵1 The abbreviations used are:
- K
channel -
ATP-sensitive K
channel
- AMP-PNP
-
adenyl-5′-yl imidodiphosphate
- ACTH
-
corticotropin.
- K
-
- Received December 5, 1994.
- Revision received January 9, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
