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BMC Physiology
Published in: BMC Physiology 1/2005

Open Access 01-12-2005 | Research article

Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature

Authors: Alison Morrissey, Erika Rosner, Jennifer Lanning, Lavanya Parachuru, Piyali Dhar Chowdhury, Sandra Han, Gwendolyn Lopez, XiaoYong Tong, Hidetada Yoshida, Tomoe Y Nakamura, Michael Artman, Jonathan P Giblin, Andrew Tinker, William A Coetzee

Published in: BMC Physiology | Issue 1/2005

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Abstract

Background

Electrophysiological data suggest that cardiac KATP channels consist of Kir6.2 and SUR2A subunits, but the distribution of these (and other KATP channel subunits) is poorly defined. We examined the localization of each of the KATP channel subunits in the mouse and rat heart.

Results

Immunohistochemistry of cardiac cryosections demonstrate Kir6.1 protein to be expressed in ventricular myocytes, as well as in the smooth muscle and endothelial cells of coronary resistance vessels. Endothelial capillaries also stained positive for Kir6.1 protein. Kir6.2 protein expression was found predominantly in ventricular myocytes and also in endothelial cells, but not in smooth muscle cells. SUR1 subunits are strongly expressed at the sarcolemmal surface of ventricular myocytes (but not in the coronary vasculature), whereas SUR2 protein was found to be localized predominantly in cardiac myocytes and coronary vessels (mostly in smaller vessels). Immunocytochemistry of isolated ventricular myocytes shows co-localization of Kir6.2 and SUR2 proteins in a striated sarcomeric pattern, suggesting t-tubular expression of these proteins. Both Kir6.1 and SUR1 subunits were found to express strongly at the sarcolemma. The role(s) of these subunits in cardiomyocytes remain to be defined and may require a reassessment of the molecular nature of ventricular KATP channels.

Conclusions

Collectively, our data demonstrate unique cellular and subcellular KATP channel subunit expression patterns in the heart. These results suggest distinct roles for KATP channel subunits in diverse cardiac structures.
Appendix
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Literature
1.
Samaha FF, Heineman FW, Ince C, Fleming J, Balaban RS: ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo. Am J Physiol. 1992, 262: C1220-C1227.PubMed
2.
Quayle JM, Dart C, Standen NB: The properties and distribution of inward rectifier potassium currents in pig coronary arterial smooth muscle. J Physiol (Lond). 1996, 494: 715-726.CrossRef
3.
Nilius B, Viana F, Droogmans G: Ion channels in vascular endothelium. Annu Rev Physiol. 1997, 59: 145-170. 10.1146/annurev.physiol.59.1.145.CrossRefPubMed
4.
Paucek P, Mironova G, Mahdi F, Beavis AD, Woldegiorgis G, Garlid KD: Reconstitution and partial purification of the glibenclamide-sensitive, ATP-dependent K+-channel from rat liver and beef heart mitochondria. J Biol Chem. 1992, 267: 26062-26069.PubMed
5.
Seino S, Miki T: Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol. 2003, 81: 133-176. 10.1016/S0079-6107(02)00053-6.CrossRefPubMed
6.
Coetzee WA, Amarillo Y, Chiu J, Chow A, McCormack T, Moreno H, Nadal M, Ozaita A, Pountney DJ, Vega-Saenz de Miera E, Rudy B: Molecular Diversity of K+ Channels. Ann N Y Acad Sci. 1999, 868: 233-285.CrossRefPubMed
7.
Inagaki N, Gonoi T, Clement JP, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J: Reconstitution of IKATP: An inward rectifier subunit plus the sulfonylurea receptor. Science. 1995, 270: 1166-1170.CrossRefPubMed
8.
Yokoshiki H, Sunagawa M, Seki T, Sperelakis N: Antisense oligodeoxynucleotides of sulfonylurea receptors inhibit ATP-sensitive K+ channels in cultured neonatal rat ventricular cells. Pflugers Arch. 1999, 437: 400-408. 10.1007/s004240050794.CrossRefPubMed
9.
Miki T, Suzuki M, Shibasaki T, Uemura H, Sato T, Yamaguchi K, Koseki H, Iwanaga T, Nakaya H, Seino S: Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1. Nat Med. 2002, 8: 466-472. 10.1038/nm0502-466.CrossRefPubMed
10.
Baron A, van Bever L, Monnier D, Roatti A, Baertschi AJ: A novel K(ATP) current in cultured neonatal rat atrial appendage cardiomyocytes. Circ Res. 1999, 85: 707-715.CrossRefPubMed
11.
Akao M, Otani H, Horie M, Takano M, Kuniyasu A, Nakayama H, Kouchi I, Murakami T, Sasayama S: Myocardial ischemia induces differential regulation of KATP channel gene expression in rat hearts. J Clin Invest. 1997, 100: 3053-3059.PubMedCentralCrossRefPubMed
12.
Lu CW, Halvorsen SW: Channel activators regulate ATP-sensitive potassium channel (Kir6.1) expression in chick cardiomyocytes. FEBS lett. 1997, 412: 121-125. 10.1016/S0014-5793(97)00760-6.CrossRefPubMed
13.
Yoshida H, Feig J, Ghiu IA, Artman M, Coetzee WA: Native K(ATP) Channels in Human Coronary Artery Endothelial Cells consist of a Heteromultimeric Complex of Kir6.1, Kir6.2, and SUR2B Subunits. J Mol Cell Cardiol. 2004, 37: 857-869. 10.1016/j.yjmcc.2004.05.022.CrossRefPubMed
14.
Cui Y, Giblin JP, Clapp LH, Tinker A: A mechanism for ATP-sensitive potassium channel diversity: Functional coassembly of two pore-forming subunits. Proc Natl Acad Sci U S A. 2001, 98: 729-734. 10.1073/pnas.011370498.PubMedCentralCrossRefPubMed
15.
Morrissey A, Parachuru L, Lopez G, Nakamura TY, Giblin JP, Dhar Chowdhury P, Yoshida H, Artman M, Coetzee WA: Expression of K(ATP) Channel Subunits during Perinatal Maturation in the Mouse Heart. Pediatr Res. 2004,
16.
Brock R, Hamelers IH, Jovin TM: Comparison of fixation protocols for adherent cultured cells applied to a GFP fusion protein of the epidermal growth factor receptor. Cytometry. 1999, 35: 353-362. 10.1002/(SICI)1097-0320(19990401)35:4<353::AID-CYTO8>3.0.CO;2-M.CrossRefPubMed
17.
18.
Chutkow WA, Simon MC, Le Beau MM, Burant CF: Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle, and vascular KATP channels. Diabetes. 1996, 45: 1439-1445.CrossRefPubMed
19.
20.
Babenko AP, Gonzalez G, Aguilar-Bryan L, Bryan J: Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells. Circ Res. 1998, 83: 1132-1143.CrossRefPubMed
21.
Miki T, Nagashima K, Tashiro F, Kotake K, Yoshitomi H, Tamamoto A, Gonoi T, Iwanaga T, Miyazaki J, Seino S: Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Proc Natl Acad Sci USA. 1998, 95: 10402-10406. 10.1073/pnas.95.18.10402.PubMedCentralCrossRefPubMed
22.
Chutkow WA, Samuel V, Hansen PA, Pu J, Valdivia CR, Makielski JC, Burant CF: Disruption of Sur2-containing K(ATP) channels enhances insulin-stimulated glucose uptake in skeletal muscle. Proc Natl Acad Sci U S A. 2001, 98: 11760-11764. 10.1073/pnas.201390398.PubMedCentralCrossRefPubMed
23.
Singh H, Hudman D, Lawrence CL, Rainbow RD, Lodwick D, Norman RI: Distribution of Kir6.0 and SUR2 ATP-sensitive potassium channel subunits in isolated ventricular myocytes. J Mol Cell Cardiol. 2003, 35: 445-459. 10.1016/S0022-2828(03)00041-5.CrossRefPubMed
24.
Korchev YE, Negulyaev YA, Edwards CR, Vodyanoy I, Lab MJ: Functional localization of single active ion channels on the surface of a living cell. Nat Cell Biol. 2000, 2: 616-619. 10.1038/35023563.CrossRefPubMed
25.
Satoh E, Yanagisawa T, Taira N: Specific antagonism by glibenclamide of negative inotropic effects of potassium channel openers in canine atrial muscle. Jpn J Pharmacol. 1990, 54: 133-141.CrossRefPubMed
26.
Melamed-Frank M, Terzic A, Carrasco AJ, Nevo E, Avivi A, Levy AP: Reciprocal regulation of expression of pore-forming KATP channel genes by hypoxia. Mol Cell Biochem. 2001, 225: 145-150. 10.1023/A:1012286624993.CrossRefPubMed
27.
Garlid KD, Paucek P, Yarov-Yarovoy V, Murray HN, Darbenzio RB, D'Alonzo AJ, Lodge NJ, Smith MA, Grover GJ: Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+ channels. Possible mechanism of cardioprotection. Circ Res. 1997, 81: 1072-1082.CrossRefPubMed
28.
Liu Y, Sato T, O'Rourke B, Marban E: Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?. Circulation. 1998, 97: 2463-2469.CrossRefPubMed
29.
Suzuki M, Kotake K, Fujikura K, Inagaki N, Suzuki T, Gonoi T, Seino S, Takata K: Kir6.1: A possible subunit of ATP-sensitive K+ channels in mitochondria. Biochem Biophys Res Commun. 1997, 241: 693-697. 10.1006/bbrc.1997.7891.CrossRefPubMed
30.
Lacza Z, Snipes JA, Miller AW, Szabo C, Grover G, Busija DW: Heart mitochondria contain functional ATP-dependent K+ channels. J Mol Cell Cardiol. 2003, 35: 1339-1347. 10.1016/S0022-2828(03)00249-9.CrossRefPubMed
31.
Seharaseyon J, Ohler A, Sasaki N, Fraser H, Sato T, Johns DC, O'Rourke B, Marban E: Molecular composition of mitochondrial ATP-sensitive potassium channels probed by viral Kir gene transfer. J Mol Cell Cardiol. 2000, 32: 1923-1930. 10.1006/jmcc.2000.1226.CrossRefPubMed
32.
Kuniyasu A, Kaneko K, Kawahara K, Nakayama H: Molecular assembly and subcellular distribution of ATP-sensitive potassium channel proteins in rat hearts. FEBS lett. 2003, 552: 259-263. 10.1016/S0014-5793(03)00936-0.CrossRefPubMed
33.
Quayle JM, Nelson MT, Standen NB: ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. Physiol Rev. 1997, 77: 1165-1232.PubMed
34.
Clapp LH, Tinker A: Potassium channels in the vasculature. Curr Opin Nephrol Hypertens. 1998, 7: 91-98. 10.1097/00041552-199801000-00015.PubMed
35.
Li L, Wu J, Jiang C: Differential expression of Kir6.1 and SUR2B mRNAs in the vasculature of various tissues in rats. J Membr Biol. 2003, 196: 61-69. 10.1007/s00232-003-0625-z.CrossRefPubMed
36.
Chutkow WA, Pu J, Wheeler MT, Wada T, Makielski JC, Burant CF, McNally EM: Episodic coronary artery vasospasm and hypertension develop in the absence of Sur2 K(ATP) channels. J Clin Invest. 2002, 110: 203-208. 10.1172/JCI200215672.PubMedCentralCrossRefPubMed
37.
Hutcheson IR, Griffith TM: Heterogeneous populations of K+ channels mediate EDRF release to flow but not agonists in rabbit aorta. Am J Physiol. 1994, 266: H590-H596.PubMed
38.
Ishizaka H, Kuo L: Endothelial ATP-sensitive potassium channels mediate coronary microvascular dilation to hyperosmolarity. Am J Physiol. 1997, 273: H104-H112.PubMed
39.
Ishizaka H, Gudi SR, Frangos JA, Kuo L: Coronary arteriolar dilation to acidosis: role of ATP-sensitive potassium channels and pertussis toxin-sensitive G proteins. Circulation. 1999, 99: 558-563.CrossRefPubMed
40.
Kuo L, Chancellor JD: Adenosine potentiates flow-induced dilation of coronary arterioles by activating KATP channels in endothelium. Am J Physiol. 1995, 269: H541-H549.PubMed
41.
Schnitzler MM, Derst C, Daut J, Preisig-Muller R: ATP-sensitive potassium channels in capillaries isolated from guinea-pig heart. J Physiol (Lond). 2000, 525: 307-317. 10.1111/j.1469-7793.2000.t01-1-00307.x.CrossRef
42.
Pond AL, Scheve BK, Benedict AT, Petrecca K, Van Wagoner DR, Shrier A, Nerbonne JM: Expression of distinct ERG proteins in rat, mouse, and human heart. Relation to functional IKr channels. J Biol Chem. 2000, 275: 5997-6006. 10.1074/jbc.275.8.5997.CrossRefPubMed
Metadata
Title
Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature
Authors
Alison Morrissey
Erika Rosner
Jennifer Lanning
Lavanya Parachuru
Piyali Dhar Chowdhury
Sandra Han
Gwendolyn Lopez
XiaoYong Tong
Hidetada Yoshida
Tomoe Y Nakamura
Michael Artman
Jonathan P Giblin
Andrew Tinker
William A Coetzee
Publication date
01-12-2005
Publisher
BioMed Central
Published in
BMC Physiology / Issue 1/2005
Electronic ISSN: 1472-6793
DOI
https://doi.org/10.1186/1472-6793-5-1

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