Circulation Research. 2001;89:944-956
doi: 10.1161/hh2301.100349
doi: 10.1161/hh2301.100349
© 2001 American Heart Association, Inc.
Reviews |
Genetic Manipulation of Cardiac K+ Channel Function in Mice
What Have We Learned, and Where Do We Go From Here?
From the Departments of Molecular Biology and Pharmacology (J.M.N.) and Cell Biology and Physiology (C.G.N.), Washington University Medical School, St Louis, Mo; the Division of Neuroscience (T.L.S.), Children’s Hospital and Harvard Medical School, Boston, Mass; and INSERM U533 (D.E.), Hôpital Hotel-Dieu, Nantes, France.
Correspondence to Denis Escande, Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Moléculaires, INSERM U533, 1 rue Gaston Veil, Faculté de Médecine, 44035 Nantes, France. E-mail denis.escande{at}nantes.inserm.fr
Abstract
In the mammalian myocardium, potassium (K+) channels control resting potentials, action potential waveforms, automaticity, and refractory periods and, in most cardiac cells, multiple types of K+ channels that subserve these functions are expressed. Molecular cloning has revealed the presence of a large number of K+ channel pore forming (
) and accessory (ß) subunits in the heart, and considerable progress has been made recently in defining the relationships between expressed K+ channel subunits and functional cardiac K+ channels. To date, more than 20 mouse models with altered K+ channel expression/functioning have been generated using dominant-negative transgenic and targeted gene deletion approaches. In several instances, the genetic manipulation of K+ channel subunit expression has revealed the role of specific K+ channel subunit subfamilies or individual K+ channel subunit genes in the generation of myocardial K+ channels. In other cases, however, the phenotypic consequences have been unexpected. This review summarizes what has been learned from the in situ genetic manipulation of cardiac K+ channel functioning in the mouse, discusses the limitations of the models developed to date, and explores the likely directions of future research.
Key Words: Ito • IK • IK1 • mouse models • cardiac remodeling
This article has been cited by other articles:
 |
|
 |
|
  M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mertens, O. Stiedl, S. Steinlechner, and M. Meyer Cardiac dynamics during daily torpor in the Djungarian hamster (Phodopus sungorus) Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R639 - R650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Abriel Roles and regulation of the cardiac sodium channel Nav1.5: Recent insights from experimental studies Cardiovasc Res, December 1, 2007; 76(3): 381 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Putzke, P. J. Hanley, G. Schlichthorl, R. Preisig-Muller, S. Rinne, M. Anetseder, R. Eckenhoff, C. Berkowitz, T. Vassiliou, H. Wulf, et al. Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1 Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1319 - C1326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. E. Bondarenko and R. L. Rasmusson Simulations of propagated mouse ventricular action potentials: effects of molecular heterogeneity Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1816 - H1832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Qu, V. E. Bondarenko, C. Xie, S. Wang, M. S. Awayda, H. C. Strauss, and M. J. Morales W-7 modulates Kv4.3: pore block and Ca2+-calmodulin inhibition Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2364 - H2377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Salama and B. London Mouse models of long QT syndrome J. Physiol., January 1, 2007; 578(1): 43 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Thomas, M. J. Killeen, I. S. Gurung, P. Hakim, R. Balasubramaniam, C. A. Goddard, A. A. Grace, and C. L.-H. Huang Mechanisms of ventricular arrhythmogenesis in mice following targeted disruption of KCNE1 modelling long QT syndrome 5 J. Physiol., January 1, 2007; 578(1): 99 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, C. Marionneau, R. Zhang, V. Shah, J. W. Hell, J. M. Nerbonne, and M. E. Anderson Calmodulin Kinase II Inhibition Shortens Action Potential Duration by Upregulation of K+ Currents Circ. Res., November 10, 2006; 99(10): 1092 - 1099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wang, V. E. Bondarenko, Y.-j. Qu, G. C. L. Bett, M. J. Morales, R. L. Rasmusson, and H. C. Strauss Time- and Voltage-Dependent Components of Kv4.3 Inactivation Biophys. J., November 1, 2005; 89(5): 3026 - 3041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Nerbonne and R. S. Kass Molecular Physiology of Cardiac Repolarization Physiol Rev, October 1, 2005; 85(4): 1205 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Tamarina, A. Kuznetsov, L. E. Fridlyand, and L. H. Philipson Delayed-rectifier (KV2.1) regulation of pancreatic {beta}-cell calcium responses to glucose: inhibitor specificity and modeling Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E578 - E585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Milan and C. A. MacRae Animal models for arrhythmias Cardiovasc Res, August 15, 2005; 67(3): 426 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Demolombe, C. Marionneau, S. Le Bouter, F. Charpentier, and D. Escande Functional genomics of cardiac ion channel genes Cardiovasc Res, August 15, 2005; 67(3): 438 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wang, M. Shahidullah, C. A. Rocha, C. Strang, P. J. Pfaffinger, and M. Covarrubias Functionally Active T1-T1 Interfaces Revealed by the Accessibility of Intracellular Thiolate Groups in Kv4 Channels J. Gen. Physiol., June 27, 2005; 126(1): 55 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Harris, G. D. Mills, X. Chen, H. Kubo, R. M. Berretta, V. S. Votaw, L. F. Santana, and S. R. Houser Alterations in Early Action Potential Repolarization Causes Localized Failure of Sarcoplasmic Reticulum Ca2+ Release Circ. Res., March 18, 2005; 96(5): 543 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Mosca, R. A. Carrillo, B. H. White, and H. Keshishian Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K+ channel subunit PNAS, March 1, 2005; 102(9): 3477 - 3482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-C. Chiu, A. Kovacs, R. M. Blanton, X. Han, M. Courtois, C. J. Weinheimer, K. A. Yamada, S. Brunet, H. Xu, J. M. Nerbonne, et al. Transgenic Expression of Fatty Acid Transport Protein 1 in the Heart Causes Lipotoxic Cardiomyopathy Circ. Res., February 4, 2005; 96(2): 225 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Royer, S. Demolombe, A. El Harchi, K. Le Quang, J. Piron, G. Toumaniantz, D. Mazurais, C. Bellocq, G. Lande, C. Terrenoire, et al. Expression of human ERG K+ channels in the mouse heart exerts anti-arrhythmic activity Cardiovasc Res, January 1, 2005; 65(1): 128 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nygren, A. E. Lomax, and W. R. Giles Heterogeneity of action potential durations in isolated mouse left and right atria recorded using voltage-sensitive dye mapping Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2634 - H2643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Caballero, R. Gomez, L. Nunez, I. Moreno, J. Tamargo, and E. Delpon Diltiazem inhibits hKv1.5 and Kv4.3 currents at therapeutic concentrations Cardiovasc Res, December 1, 2004; 64(3): 457 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Perrier, R. Perrier, S. Richard, and J.-P. Benitah Ca2+ Controls Functional Expression of the Cardiac K+ Transient Outward Current via the Calcineurin Pathway J. Biol. Chem., September 24, 2004; 279(39): 40634 - 40639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. E. Bondarenko, G. P. Szigeti, G. C. L. Bett, S.-J. Kim, and R. L. Rasmusson Computer model of action potential of mouse ventricular myocytes Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1378 - H1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Brunet, F. Aimond, H. Li, W. Guo, J. Eldstrom, D. Fedida, K. A. Yamada, and J. M. Nerbonne Heterogeneous expression of repolarizing, voltage-gated K+ currents in adult mouse ventricles J. Physiol., August 15, 2004; 559(1): 103 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yamashita, H. Kohzuki, Y. Kitagawa, T. Nakashima, A. Kikuta, and M. Takaki O2 consumption of mechanically unloaded contractions of mouse left ventricular myocardial slices Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H54 - H62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, V. E. Bondarenko, Y. Qu, M. J. Morales, R. L. Rasmusson, and H. C. Strauss Activation properties of Kv4.3 channels: time, voltage and [K+]o dependence J. Physiol., June 15, 2004; 557(3): 705 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yamamoto-Mizuma, G.-X. Wang, L. L. Liu, K. Schegg, W. J. Hatton, D. Duan, T. L. B. Horowitz, F. S. Lamb, and J. R. Hume Altered properties of volume-sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3-/- mice J. Physiol., June 1, 2004; 557(2): 439 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rosati and D. McKinnon Regulation of Ion Channel Expression Circ. Res., April 16, 2004; 94(7): 874 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. X. Liu, J. Zhou, S. Nattel, and G. Koren Single-channel recordings of a rapid delayed rectifier current in adult mouse ventricular myocytes: basic properties and effects of divalent cations J. Physiol., April 15, 2004; 556(2): 401 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Fountain, A. Cheong, R. Flemming, L. Mair, A. Sivaprasadarao, and D. J. Beech Functional up-regulation of KCNA gene family expression in murine mesenteric resistance artery smooth muscle J. Physiol., April 1, 2004; 556(1): 29 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. Flagg, F. Charpentier, J. Manning-Fox, M. S. Remedi, D. Enkvetchakul, A. Lopatin, J. Koster, and C. Nichols Remodeling of excitation-contraction coupling in transgenic mice expressing ATP-insensitive sarcolemmal KATP channels Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1361 - H1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Malinowska, A. M. Sherry, K. P. Tewari, and J. Cuppoletti Gastric parietal cell secretory membrane contains PKA- and acid-activated Kir2.1 K+ channels Am J Physiol Cell Physiol, March 1, 2004; 286(3): C495 - C506. [Abstract] [Full Text]
|
|
|
|
|
|
G. Liu, J. B. Iden, K. Kovithavongs, R. Gulamhusein, H. J. Duff, and K. M. Kavanagh In vivo temporal and spatial distribution of depolarization and repolarization and the illusive murine T wave J. Physiol., February 15, 2004; 555(1): 267 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Lomax, C. S. Kondo, and W. R. Giles Comparison of time- and voltage-dependent K+ currents in myocytes from left and right atria of adult mice Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1837 - H1848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Lees-Miller, J. Guo, J. R. Somers, D. E. Roach, R. S. Sheldon, D. E. Rancourt, and H. J. Duff Selective Knockout of Mouse ERG1 B Potassium Channel Eliminates IKr in Adult Ventricular Myocytes and Elicits Episodes of Abrupt Sinus Bradycardia Mol. Cell. Biol., March 15, 2003; 23(6): 1856 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Probst, F. Kyndt, F. Potet, J.-N. Trochu, G. Mialet, S. Demolombe, J.-J. Schott, I. Baro, D. Escande, and H. Le Marec Haploinsufficiency in combination with aging causes SCN5A-linked hereditary Lenegre disease J. Am. Coll. Cardiol., February 19, 2003; 41(4): 643 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Alseikhan, C. D. DeMaria, H. M. Colecraft, and D. T. Yue Engineered calmodulins reveal the unexpected eminence of Ca2+ channel inactivation in controlling heart excitation PNAS, December 24, 2002; 99(26): 17185 - 17190. [Abstract] [Full Text] [PDF]
|
|