1. KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts.
- Author
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Jiang M, Zhang M, Tang DG, Clemo HF, Liu J, Holwitt D, Kasirajan V, Pond AL, Wettwer E, and Tseng GN
- Subjects
- Aging metabolism, Animals, COS Cells, Chlorocebus aethiops, Disease Models, Animal, Dogs, ERG1 Potassium Channel, Ether-A-Go-Go Potassium Channels, Heart Conduction System physiopathology, Heart Ventricles pathology, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Ion Channels metabolism, Ion Transport, Long QT Syndrome metabolism, Macromolecular Substances, Male, Muscle Proteins metabolism, Myocardial Ischemia metabolism, Myocardium metabolism, Potassium Channels analysis, Potassium Channels genetics, Potassium Channels metabolism, Protein Subunits, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Species Specificity, Transfection, Heart Ventricles metabolism, Potassium metabolism, Potassium Channels physiology, Potassium Channels, Voltage-Gated, Ventricular Remodeling physiology
- Abstract
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 (beta) 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, alpha, 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 alpha-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.
- Published
- 2004
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