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(Circulation. 2004;109:1783-1788.)
© 2004 American Heart Association, Inc.

Basic Science Reports

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; 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.).

Correspondence to Gea-Ny Tseng, PhD, Department of Physiology, Virginia Commonwealth University, 1101 E Marshall St, Richmond, VA 23298. E-mail gtseng{at}hsc.vcu.edu

Received June 24, 2003; de novo received November 18, 2003; accepted December 22, 2003.

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 (ß) 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

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