Regulation of KChIP2 potassium channel {beta} subunit gene expression underlies the gradient of transient outward current in canine and human ventricle

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Regulation of KChIP2 potassium channel $beta$ subunit gene expression underlies the gradient of transient outward current in canine and human ventricle

Barbara Rosati †, Zongming Pan ‡, Steven Lypen ‡, Hong-Sheng Wang †, Ira Cohen †, Jane E. Dixon † and David McKinnon *‡

* Institute of Molecular Cardiology, † Department of Physiology and Biophysics and ‡ Department of Neurobiology and Behavior, State University of New York, Stony Brook, NY 11794, USA

Expression of four members of the KChIP family of potassium channel $beta$ subunits was examined in canine heart. Only one member of the gene family, KChIP2, was expressed in heart.
There was a steep gradient of KChIP2 mRNA expression across the canine ventricular free wall. KChIP2 mRNA was 25-fold more abundant in the epicardium than in the endocardium, and this gradient paralleled the gradient in transient outward current (I_to) expression. In contrast, Kv4.3 potassium channel $alpha$ subunit mRNA was expressed at equal levels across the ventricular wall.
There was no difference in the pharmacological sensitivity of epicardial and endocardial I_to channels to flecainide, suggesting that the current is produced by the same channel in the two tissues.
A similar gradient of KChIP2 expression was found across the ventricular wall of human heart, but not rat heart.
It is concluded that transcriptional regulation of the KChIP2 $beta$ subunit gene, rather than the Kv4.3 $alpha$ subunit gene, is the primary determinant regulating the transmural gradient of I_to expression in the ventricular free wall of canine and human heart.

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				N. Gong, I. Bodi, C. Zobel, A. Schwartz, J. D. Molkentin, and P. H. Backx Calcineurin Increases Cardiac Transient Outward K+ Currents via Transcriptional Up-regulation of Kv4.2 Channel Subunits J. Biol. Chem., December 15, 2006; 281(50): 38498 - 38506. [Abstract] [Full Text] [PDF]

				S. N. Flaim, W. R. Giles, and A. D. McCulloch Contributions of sustained INa and IKv43 to transmural heterogeneity of early repolarization and arrhythmogenesis in canine left ventricular myocytes Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2617 - H2629. [Abstract] [Full Text] [PDF]

				C. ANTZELEVITCH Cellular Basis for the Repolarization Waves of the ECG Ann. N.Y. Acad. Sci., October 1, 2006; 1080(1): 268 - 281. [Abstract] [Full Text] [PDF]

				W. Han, S. Nattel, T. Noguchi, and A. Shrier C-terminal Domain of Kv4.2 and Associated KChIP2 Interactions Regulate Functional Expression and Gating of Kv4.2 J. Biol. Chem., September 15, 2006; 281(37): 27134 - 27144. [Abstract] [Full Text] [PDF]

				S. Radicke, D. Cotella, E. M. Graf, U. Banse, N. Jost, A. Varro, G.-N. Tseng, U. Ravens, and E. Wettwer Functional modulation of the transient outward current Ito by KCNE {beta}-subunits and regional distribution in human non-failing and failing hearts Cardiovasc Res, September 1, 2006; 71(4): 695 - 703. [Abstract] [Full Text] [PDF]

				M. N. Obreztchikova, K. W. Patberg, A. N. Plotnikov, N. Ozgen, I. N. Shlapakova, A. V. Rybin, E. A. Sosunov, P. Danilo Jr., E. P. Anyukhovsky, R. B. Robinson, et al. IKr contributes to the altered ventricular repolarization that determines long-term cardiac memory Cardiovasc Res, July 1, 2006; 71(1): 88 - 96. [Abstract] [Full Text] [PDF]

				Y. Li, S. Y. Um, and T. V. Mcdonald Voltage-Gated Potassium Channels: Regulation by Accessory Subunits Neuroscientist, June 1, 2006; 12(3): 199 - 210. [Abstract] [PDF]

				C. F. Rossow, K. W. Dilly, and L. F. Santana Differential Calcineurin/NFATc3 Activity Contributes to the Ito Transmural Gradient in the Mouse Heart Circ. Res., May 26, 2006; 98(10): 1306 - 1313. [Abstract] [Full Text] [PDF]

				A. S. Barth and S. Kaab MAPK = Mitogen-Activated Protein KChIP2?: Unraveling Signaling Pathways Controlling Cardiac Ito Expression Circ. Res., February 17, 2006; 98(3): 301 - 302. [Full Text] [PDF]

				Y. Jia and K. Takimoto Mitogen-Activated Protein Kinases Control Cardiac KChIP2 Gene Expression Circ. Res., February 17, 2006; 98(3): 386 - 393. [Abstract] [Full Text] [PDF]

				V. Salvador-Recatala, W. J. Gallin, J. Abbruzzese, P. C. Ruben, and A. N. Spencer A potassium channel (Kv4) cloned from the heart of the tunicate Ciona intestinalis and its modulation by a KChIP subunit J. Exp. Biol., February 15, 2006; 209(4): 731 - 747. [Abstract] [Full Text] [PDF]

				W. Guo, W. E. Jung, C. Marionneau, F. Aimond, H. Xu, K. A. Yamada, T. L. Schwarz, S. Demolombe, and J. M. Nerbonne Targeted Deletion of Kv4.2 Eliminates Ito,f and Results in Electrical and Molecular Remodeling, With No Evidence of Ventricular Hypertrophy or Myocardial Dysfunction Circ. Res., December 9, 2005; 97(12): 1342 - 1350. [Abstract] [Full Text] [PDF]

				S. P. Patel and D. L. Campbell Transient outward potassium current, 'Ito', phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms J. Physiol., November 15, 2005; 569(1): 7 - 39. [Abstract] [Full Text] [PDF]

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Regulation of KChIP2 potassium channel subunit gene expression underlies the gradient of transient outward current in canine and human ventricle

Barbara Rosati *†, Zongming Pan *‡, Steven Lypen *‡, Hong-Sheng Wang *†, Ira Cohen *†, Jane E. Dixon *† and David McKinnon *‡

Regulation of KChIP2 potassium channel $beta$ subunit gene expression underlies the gradient of transient outward current in canine and human ventricle

Barbara Rosati †, Zongming Pan ‡, Steven Lypen ‡, Hong-Sheng Wang †, Ira Cohen †, Jane E. Dixon † and David McKinnon *‡

				J. Rose, A. A. Armoundas, Y. Tian, D. DiSilvestre, M. Burysek, V. Halperin, B. O'Rourke, D. A. Kass, E. Marban, and G. F. Tomaselli Molecular correlates of altered expression of potassium currents in failing rabbit myocardium Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2077 - H2087. [Abstract] [Full Text] [PDF]

				M. Gallego, R. Setien, L. Puebla, M. d. C. Boyano-Adanez, E. Arilla, and O. Casis {alpha}1-Adrenoceptors stimulate a G{alpha}s protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart Am J Physiol Cell Physiol, March 1, 2005; 288(3): C577 - C585. [Abstract] [Full Text] [PDF]

				N. Szentadrassy, T. Banyasz, T. Biro, G. Szabo, B. I. Toth, J. Magyar, J. Lazar, A. Varro, L. Kovacs, and P. P. Nanasi Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium Cardiovasc Res, March 1, 2005; 65(4): 851 - 860. [Abstract] [Full Text] [PDF]

				S. Zicha, L. Xiao, S. Stafford, T. J. Cha, W. Han, A. Varro, and S. Nattel Transmural expression of transient outward potassium current subunits in normal and failing canine and human hearts J. Physiol., December 15, 2004; 561(3): 735 - 748. [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]

				S. V. Doronin, I. A. Potapova, Z. Lu, and I. S. Cohen Angiotensin Receptor Type 1 Forms a Complex with the Transient Outward Potassium Channel Kv4.3 and Regulates Its Gating Properties and Intracellular Localization J. Biol. Chem., November 12, 2004; 279(46): 48231 - 48237. [Abstract] [Full Text] [PDF]

				R. A. Bassani, J. Altamirano, J. L. Puglisi, and D. M. Bers Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes J. Physiol., September 1, 2004; 559(2): 593 - 609. [Abstract] [Full Text] [PDF]

				Y. Wakisaka, S. Niwano, H. Niwano, J. Saito, T. Yoshida, S. Hirasawa, H. Kawada, and T. Izumi Structural and electrical ventricular remodeling in rat acute myocarditis and subsequent heart failure Cardiovasc Res, September 1, 2004; 63(4): 689 - 699. [Abstract] [Full Text] [PDF]

				A. N. Plotnikov, E. A. Sosunov, K. W. Patberg, E. P. Anyukhovsky, R. Z. Gainullin, I. N. Shlapakova, G. Krishnamurthy, P. Danilo Jr, and M. R. Rosen Cardiac Memory Evolves With Age in Association With Development of the Transient Outward Current Circulation, August 3, 2004; 110(5): 489 - 495. [Abstract] [Full Text] [PDF]

				S. G. Birnbaum, A. W. Varga, L.-L. Yuan, A. E. Anderson, J. D. Sweatt, and L. A. Schrader Structure and Function of Kv4-Family Transient Potassium Channels Physiol Rev, July 1, 2004; 84(3): 803 - 833. [Abstract] [Full Text] [PDF]