© 1995 American Heart Association, Inc.
Articles |
Cloning and Functional Expression of an Inwardly Rectifying K+ Channel From Human Atrium
From the Department of Molecular Physiology and Biophysics (B.A.W., M. De B., K.M.), Baylor College of Medicine, Houston, Tex; the Department of Pharmacology "E. Meneghetti" (M. De B.), University of Padua (Italy); the Department of Human Communication Science–Section of Pharmacology (M.T.), Second School of Medicine, University of Naples (Italy); and Rammelkamp Center (A.M.B.), Metro Health System, and Department of Physiology, Case Western Reserve University, Cleveland, Ohio.
Correspondence to Dr Barbara A. Wible, Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
Abstract The cardiac inward rectifier current (IK1) contributes to the shape and duration of the cardiac action potential and helps to set the resting membrane potential. Although several inwardly rectifying K+ channels (IRKs) from different tissues have been cloned recently, the nature and number of K+ channels contributing to the cardiac IK1 are presently unknown. To address this issue in human heart, we have used the reverse-transcriptase–polymerase chain reaction (PCR) technique with human atrial total RNA as a template to identify two sequences expressed in heart that are homologous to previously cloned IRKs. One of the PCR products we obtained was virtually identical to IRK1 (cloned from a mouse macrophage cell line); the other, which we named hIRK, exhibited <70% identity to IRK1. A full-length clone encoding hIRK was isolated from a human atrial cDNA library and functionally expressed in Xenopus oocytes. This channel, like IRK1, exhibited strong inward rectification and was blocked by divalent cations. However, hIRK differed from IRK1 at the single-channel level: hIRK had a single-channel conductance of 36 pS compared with 21 pS for IRK1. We have identified single channels of 41, 35, 21, and 9 pS in recordings from dispersed human atrial myocytes. However, none of these atrial inward rectifiers exhibited single-channel properties exactly like those of cloned hIRK expressed in oocytes. Our findings suggest that the cardiac IK1 in human atrial myocytes is composed of multiple inwardly rectifying channels distinguishable on the basis of single-channel conductance, each of which may be the product of a different gene.
Key Words: human cardiac myocytes • human atrium • K+ channels • inward rectifiers
This article has been cited by other articles:
 |
|
 |
|
  A. L. Vega, D. J. Tester, M. J. Ackerman, and J. C. Makielski Protein Kinase A-Dependent Biophysical Phenotype for V227F-KCNJ2 Mutation in Catecholaminergic Polymorphic Ventricular Tachycardia Circ Arrhythm Electrophysiol, October 1, 2009; 2(5): 540 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tikku, Y. Epshtein, H. Collins, A. J. Travis, G. H. Rothblat, and I. Levitan Relationship between Kir2.1/Kir2.3 activity and their distributions between cholesterol-rich and cholesterol-poor membrane domains Am J Physiol Cell Physiol, July 1, 2007; 293(1): C440 - C450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rajamani, C. L. Anderson, C. R. Valdivia, L. L. Eckhardt, J. D. Foell, G. A. Robertson, T. J. Kamp, J. C. Makielski, B. D. Anson, and C. T. January Specific serine proteases selectively damage KCNH2 (hERG1) potassium channels and IKr Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1278 - H1288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-H. Yan, K. Nishimura, K. Yoshida, K. Nakahira, T. Ehara, K. Igarashi, and K. Ishihara Different intracellular polyamine concentrations underlie the difference in the inward rectifier K+ currents in atria and ventricles of the guinea-pig heart J. Physiol., March 15, 2005; 563(3): 713 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Zitron, C. Kiesecker, S. Luck, S. Kathofer, D. Thomas, V. A.W Kreye, J. Kiehn, H. A Katus, W. Schoels, and C. A Karle Human cardiac inwardly rectifying current IKir2.2 is upregulated by activation of protein kinase A Cardiovasc Res, August 15, 2004; 63(3): 520 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tamargo, R. Caballero, R. Gomez, C. Valenzuela, and E. Delpon Pharmacology of cardiac potassium channels Cardiovasc Res, April 1, 2004; 62(1): 9 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Lange, F. Er, N. Gassanov, and U. C. Hoppe Andersen mutations of KCNJ2 suppress the native inward rectifier current IK1 in a dominant-negative fashion Cardiovasc Res, August 1, 2003; 59(2): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schram, M. Pourrier, Z. Wang, M. White, and S. Nattel Barium block of Kir2 and human cardiac inward rectifier currents: evidence for subunit-heteromeric contribution to native currents Cardiovasc Res, August 1, 2003; 59(2): 328 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zobel, H. C. Cho, T.-T. Nguyen, R. Pekhletski, R. J Diaz, G. J Wilson, and P. H Backx Molecular dissection of the inward rectifier potassium current (IK1) in rabbit cardiomyocytes: evidence for heteromeric co-assembly of Kir2.1 and Kir2.2 J. Physiol., July 15, 2003; 550(2): 365 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schram, P. Melnyk, M. Pourrier, Z. Wang, and S. Nattel Kir2.4 and Kir2.1 K+ channel subunits co-assemble: a potential new contributor to inward rectifier current heterogeneity J. Physiol., October 15, 2002; 544(2): 337 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Karle, E. Zitron, W. Zhang, G. Wendt-Nordahl, S. Kathofer, D. Thomas, B. Gut, E. Scholz, C.-F. Vahl, H. A. Katus, et al. Human Cardiac Inwardly-Rectifying K+ Channel Kir2.1b Is Inhibited by Direct Protein Kinase C-Dependent Regulation in Human Isolated Cardiomyocytes and in an Expression System Circulation, September 17, 2002; 106(12): 1493 - 1499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Melnyk, L. Zhang, A. Shrier, and S. Nattel Differential distribution of Kir2.1 and Kir2.3 subunits in canine atrium and ventricle Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1123 - H1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Preisig-Muller, G. Schlichthorl, T. Goerge, S. Heinen, A. Bruggemann, S. Rajan, C. Derst, R. W. Veh, and J. Daut Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome PNAS, May 28, 2002; 99(11): 7774 - 7779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Michelakis, E. K. Weir, X. Wu, A. Nsair, R. Waite, K. Hashimoto, L. Puttagunta, H. G. Knaus, and S. L. Archer Potassium channels regulate tone in rat pulmonary veins Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1138 - L1147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fischer-Lougheed, J.-H. Liu, E. Espinos, D. Mordasini, C. R. Bader, D. Belin, and L. Bernheim Human Myoblast Fusion Requires Expression of Functional Inward Rectifier Kir2.1 Channels J. Cell Biol., May 14, 2001; 153(4): 677 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Xin Liu, C. Derst, G. Schlichthorl, S. Heinen, G. Seebohm, A. Bruggemann, W. Kummer, R. W Veh, J. Daut, and R. Preisig-Muller Comparison of cloned Kir2 channels with native inward rectifier K+ channels from guinea-pig cardiomyocytes J. Physiol., April 1, 2001; 532(1): 115 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Shieh, M. Coghlan, J. P. Sullivan, and M. Gopalakrishnan Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities Pharmacol. Rev., December 1, 2000; 52(4): 557 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. I. Spencer, W. Uchida, L. Turner, and R. Z. Kozlowski Signature Currents: A Patch-Clamp Method for Determining the Selectivity of Ion-Channel Blockers in Isolated Cardiac Myocytes Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(3): 193 - 201. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yue, P. Melnyk, R. Gaspo, Z. Wang, and S. Nattel Molecular Mechanisms Underlying Ionic Remodeling in a Dog Model of Atrial Fibrillation Circ. Res., April 16, 1999; 84(7): 776 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Wang, L. Yue, M. White, G. Pelletier, and S. Nattel Differential Distribution of Inward Rectifier Potassium Channel Transcripts in Human Atrium Versus Ventricle Circulation, December 1, 1998; 98(22): 2422 - 2428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaab, J. Dixon, J. Duc, D. Ashen, M. Nabauer, D. J. Beuckelmann, G. Steinbeck, D. McKinnon, and G. F. Tomaselli Molecular Basis of Transient Outward Potassium Current Downregulation in Human Heart Failure : A Decrease in Kv4.3 mRNA Correlates With a Reduction in Current Density Circulation, October 6, 1998; 98(14): 1383 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Wible, Q. Yang, Y. A. Kuryshev, Eric. A. Accili, and A. M. Brown Cloning and Expression of a Novel K+ Channel Regulatory Protein, KChAP J. Biol. Chem., May 8, 1998; 273(19): 11745 - 11751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Y. Nakamura, M. Artman, B. Rudy, and W. A. Coetzee Inhibition of rat ventricular IK1 with antisense oligonucleotides targeted to Kir2.1 mRNA Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H892 - H900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Shuck, T. M. Piser, J. H. Bock, J. L. Slightom, K. S. Lee, and M. J. Bienkowski Cloning and Characterization of Two K+ Inward Rectifier (Kir) 1.1Potassium Channel Homologs from Human Kidney (Kir1.2 and Kir1.3) J. Biol. Chem., January 3, 1997; 272(1): 586 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kiehn, A. E. Lacerda, B. Wible, and A. M. Brown Molecular Physiology and Pharmacology of HERG: Single-Channel Currents and Block by Dofetilide Circulation, November 15, 1996; 94(10): 2572 - 2579. [Abstract] [Full Text]
|
|
|
|
|
|
D. M. Roden, R. Lazzara, M. Rosen, P. J. Schwartz, J. Towbin, and G. M. Vincent Multiple Mechanisms in the Long-QT Syndrome: Current Knowledge, Gaps, and Future Directions Circulation, October 15, 1996; 94(8): 1996 - 2012. [Abstract] [Full Text]
|
|
|
|
|
|
M. V. Brahmajothi, M. J. Morales, S. Liu, R. L. Rasmusson, D. L. Campbell, and H. C. Strauss In Situ Hybridization Reveals Extensive Diversity of K+ Channel mRNA in Isolated Ferret Cardiac Myocytes Circ. Res., June 1, 1996; 78(6): 1083 - 1089. [Abstract] [Full Text]
|
|
|
|
|
|
L. Bianchi, M.-L. Roy, M. Taglialatela, D. W. Lundgren, A. M. Brown, and E. Ficker Regulation by Spermine of Native Inward Rectifier K[IMAGE] Channels in RBL-1 Cells J. Biol. Chem., March 15, 1996; 271(11): 6114 - 6121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.G. Nichols, E.N. Makhina, W.L. Pearson, Q. Sha, and A.N. Lopatin Inward Rectification and Implications for Cardiac Excitability Circ. Res., January 1, 1996; 78(1): 1 - 7. [Abstract] [Full Text]
|
|
|
|
|
|
J. Kiehn, B. Wible, E. Ficker, M. Taglialatela, and A.M. Brown Cloned Human Inward Rectifier K+ Channel as a Target for Class III Methanesulfonanilides Circ. Res., December 1, 1995; 77(6): 1151 - 1155. [Abstract] [Full Text]
|
|