title: Expression of ATP-sensitive K+ channel subunits during perinatal maturation in the mouse heart.
abstract: Prevailing data suggest that sarcolemmal ATP-sensitive (K(ATP)) channels in the adult heart consist of Kir6.2 and SUR2A subunits, but the expression of other K(ATP) channel subunits (including SUR1, SUR2B, and Kir6.1) is poorly defined. The situation is even less clear for the immature heart, which shows a remarkable resistance to hypoxia and metabolic stress. The hypoxia-induced action potential shortening and opening of sarcolemmal K(ATP) channels that occurs in adults is less prominent in the immature heart. This might be due in part to the different biophysical and pharmacological properties of K(ATP) channels of immature and adult K(ATP) channels. Because these properties are largely conferred by subunit composition, it is important to examine the relative expression levels of the various K(ATP) channel subunits during maturation. We therefore used RNAse protection assays, reverse transcription-PCR approaches, and Western blotting to characterize the mRNA and protein expression profiles of K(ATP) channel subunits in fetal, neonatal, and adult mouse heart. Our data indicate that each of the K(ATP) channel subunits (Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B) is expressed in the mouse heart at all of the developmental time points studied. However, the expression level of each of the subunits is low in the fetal heart and progressively increases with maturation. Each of the subunits seems to be expressed in ventricular myocytes with a subcellular expression pattern matching that found in the adult. Our data suggest that the K(ATP) channel composition may change during maturation, which has important implications for K(ATP) channel function in the developing heart.
authors.affiliation: Department of Pediatrics, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Morrissey
authors.forename: Lavanya
authors.initials: L
authors.lastname: Parachuru
authors.forename: Monika
authors.initials: M
authors.lastname: Leung
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Lopez
authors.forename: Tomoe Y
authors.initials: TY
authors.lastname: Nakamura
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Tong
authors.forename: Hidetada
authors.initials: H
authors.lastname: Yoshida
authors.forename: Shekhar
authors.initials: S
authors.lastname: Srivastiva
authors.forename: Piyali Dhar
authors.initials: PD
authors.lastname: Chowdhury
authors.forename: Michael
authors.initials: M
authors.lastname: Artman
authors.forename: William A
authors.initials: WA
authors.lastname: Coetzee
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000255:Adenosine Triphosphate / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006801:Humans; D007150:Immunohistochemistry; D054086:KATP Channels; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D032342:Muscle Cells / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis*; D020033:Protein Isoforms; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011955:Receptors, Drug; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D064233:Sulfonylurea Receptors; D014018:Tissue Distribution; D014162:Transfection; D015854:Up-Regulation; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D017931:DNA Primers; D018076:DNA, Complementary; D054086:KATP Channels; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D012313:RNA; D012333:RNA, Messenger; D011955:Receptors, Drug; D012260:Ribonucleases; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human; C577510:ABCC9 protein, human; C577508:Abcc8 protein, mouse; C577511:Abcc9 protein, mouse; C092520:uK-ATP-1 potassium channel