Published Online
on April 5, 2004

A more recent version of this article appeared on April 13, 2004

This Article Full Text (PDF) Data Supplement All Versions of this Article: 109/14/1783    most recent 01.CIR.0000124225.43852.50v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jiang, M. Articles by Tseng, G.-N. Search for Related Content PubMed PubMed Citation Articles by Jiang, M. Articles by Tseng, G.-N. Related Collections Other myocardial biology Animal models of human disease Arrythmias-basic studies Physiological and pathological control of gene expression

Submitted on June 24, 2003
Revised on November 18, 2003
Accepted on December 22, 2003

KCNE2 Protein Is Expressed in Ventricles of Different Species, and Changes in Its Expression Contribute to Electrical Remodeling in Diseased Hearts

Min Jiang PhD, Mei Zhang PhD, Daniel G. Tang MD, Henry F. Clemo MD, PhD, Jie Liu PhD, Dana Holwitt MD, Vigneshwar Kasirajan MD, Amber L. Pond PhD, Erich Wettwer PhD, and Gea-Ny Tseng PhD^*

From the Departments of Physiology and Cardiology/Internal Medicine, Virginia Commonwealth University, Richmond (M.J., M.Z., H.F.C., J.L., G.-N.T.); the Division of Cardiothoracic Surgery, Virginia Commonwealth University Health System, Richmond (D.G.T., D.H., V.K.); the Medical Faculty, Dresden University of Technology, Dresden, Germany (E.W.); and the Department of Basic Medical Sciences, Purdue University, West Lafayette, Ind (A.L.P.).

^* To whom correspondence should be addressed. E-mail: gtseng{at}hsc.vcu.edu.

Background--Mutations in KCNE2 have been linked to long-QT syndrome (LQT6), yet KCNE2 protein expression in the ventricle and its functional role in native channels are not clear.

Methods and Results--We detected KCNE2 protein in human, dog, and rat ventricles in Western blot experiments. Immunocytochemistry confirmed KCNE2 protein expression in ventricular myocytes. To explore the functional role of KCNE2, we studied how its expression was altered in 2 models of cardiac pathology and whether these alterations could help explain observed changes in the function of native channels, for which KCNE2 is a putative auxiliary () subunit. In canine ventricle injured by coronary microembolizations, the rapid delayed rectifier current (I_Kr) density was increased. Although the protein level of ERG (I_Kr pore-forming, , subunit) was not altered, the KCNE2 protein level was markedly reduced. These data are consistent with the effect of heterologously expressed KCNE2 on ERG and suggest that in canine ventricle, KCNE2 may associate with ERG and suppress its current amplitude. In aging rat ventricle, the pacemaker current (I_f) density was increased. There was a significant increase in the KCNE2 protein level, whereas changes in the -subunit (HCN2) were not significant. These data are consistent with the effect of heterologously expressed KCNE2 on HCN2 and suggest that in aging rat ventricle, KCNE2 may associate with HCN2 and enhance its current amplitude.

Conclusions--KCNE2 protein is expressed in ventricles, and it can play diverse roles in ventricular electrical activity under (patho)physiological conditions.

Key words: ion channels • electrophysiology • hypertrophy

This article has been cited by other articles:

				B. Ye and J. M. Nerbonne Proteolytic Processing of HCN2 and Co-assembly with HCN4 in the Generation of Cardiac Pacemaker Channels J. Biol. Chem., September 18, 2009; 284(38): 25553 - 25559. [Abstract] [Full Text] [PDF]

				M. C. Brandt, J. Endres-Becker, N. Zagidullin, L. J. Motloch, F. Er, D. Rottlaender, G. Michels, S. Herzig, and U. C. Hoppe Effects of KCNE2 on HCN isoforms: distinct modulation of membrane expression and single channel properties Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H355 - H363. [Abstract] [Full Text] [PDF]

				M. Jiang, X. Xu, Y. Wang, F. Toyoda, X.-S. Liu, M. Zhang, R. B. Robinson, and G.-N. Tseng Dynamic Partnership between KCNQ1 and KCNE1 and Influence on Cardiac IKs Current Amplitude by KCNE2 J. Biol. Chem., June 12, 2009; 284(24): 16452 - 16462. [Abstract] [Full Text] [PDF]

				T. K. Roepke, A. Kontogeorgis, C. Ovanez, X. Xu, J. B. Young, K. Purtell, P. A. Goldstein, D. J. Christini, N. S. Peters, F. G. Akar, et al. Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f FASEB J, October 1, 2008; 22(10): 3648 - 3660. [Abstract] [Full Text] [PDF]

				C.-T. Tsai, L.-P. Lai, J.-J. Hwang, J.-L. Lin, and F.-T. Chiang Molecular Genetics of Atrial Fibrillation J. Am. Coll. Cardiol., July 22, 2008; 52(4): 241 - 250. [Abstract] [Full Text] [PDF]

				E. Gordon, G. Panaghie, L. Deng, K. J. Bee, T. K. Roepke, T. Krogh-Madsen, D. J. Christini, H. Ostrer, C. T. Basson, W. Chung, et al. A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance Cardiovasc Res, January 1, 2008; 77(1): 98 - 106. [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]

				T. K. Roepke, A. Anantharam, P. Kirchhoff, S. M. Busque, J. B. Young, J. P. Geibel, D. J. Lerner, and G. W. Abbott The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion J. Biol. Chem., August 18, 2006; 281(33): 23740 - 23747. [Abstract] [Full Text] [PDF]

				A. C.P. Wiesfeld, M. E.W. Hemels, J. P. Van Tintelen, M. P. Van den Berg, D. J. Van Veldhuisen, and I. C. Van Gelder Genetic aspects of atrial fibrillation Cardiovasc Res, August 15, 2005; 67(3): 414 - 418. [Abstract] [Full Text] [PDF]

				W. Dun and P. A. Boyden Diverse phenotypes of outward currents in cells that have survived in the 5-day-infarcted heart Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H667 - H673. [Abstract] [Full Text] [PDF]

				S. Radicke, D. Cotella, E. M. Graf, U. Ravens, and E. Wettwer Expression and function of dipeptidyl-aminopeptidase-like protein 6 as a putative {beta}-subunit of human cardiac transient outward current encoded by Kv4.3 J. Physiol., June 15, 2005; 565(3): 751 - 756. [Abstract] [Full Text] [PDF]

				J. Qu, Y. Kryukova, I. A. Potapova, S. V. Doronin, M. Larsen, G. Krishnamurthy, I. S. Cohen, and R. B. Robinson MiRP1 Modulates HCN2 Channel Expression and Gating in Cardiac Myocytes J. Biol. Chem., October 15, 2004; 279(42): 43497 - 43502. [Abstract] [Full Text] [PDF]