KCNE2
Potassium voltage-gated channel subfamily E member 2 (MinK-related peptide 1) (Minimum potassium ion channel-related peptide 1) (Potassium channel subunit beta MiRP1)
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To investigate the phosphorylation of KCNE2 protein in heart of old SHR rats. The membrane proteins from ventricular myocardium of old SHR were extracted, treated with or without alkaline phosphatase and tested binding with Ab2 (an anti-KCNE2 polyclonal antibody) by Western blot. A KCNE2 fusion protein with c-myc was obtained from in vitro translation system and treated with or without alkaline phosphatase. A series of mono- and double-point mutated fusion KCNE2 proteins with c-myc were obtained from an in vitro translation system, and Western blots with Ab2 or anti-myc antibody were performed. After alkaline phosphatase treatment, Ab2 significantly attenuated its binding with KCNE2. In vitro translation system confirmed that after alkaline phosphatase treatment, Ab2 weakened binding ability to KCNE2 while binding to c-myc was not changed. Point mutation experiments showed that serine residue in position 98 of KCNE2 proteins might be phosphorylated. KCNE2 protein in heart of old SHR rats is phosphorylated and this phosphorylation takes place in serine residue of position 98.
MeSH Terms
- Aging
- Animals
- Blotting, Western
- Hypertension
- Myocardium
- Phosphorylation
- Point Mutation
- Potassium Channels, Voltage-Gated
- Protein Binding
- Proto-Oncogene Proteins c-myc
- Rats
- Rats, Inbred SHR
- Recombinant Fusion Proteins
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. 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. KCNE2 protein is expressed in ventricles, and it can play diverse roles in ventricular electrical activity under (patho)physiological conditions.
MeSH Terms
- Aging
- Animals
- COS Cells
- Chlorocebus aethiops
- Disease Models, Animal
- Dogs
- ERG1 Potassium Channel
- Ether-A-Go-Go Potassium Channels
- Heart Conduction System
- Heart Ventricles
- Humans
- Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
- Ion Channels
- Ion Transport
- Long QT Syndrome
- Macromolecular Substances
- Male
- Muscle Proteins
- Myocardial Ischemia
- Myocardium
- Potassium
- Potassium Channels
- Potassium Channels, Voltage-Gated
- Protein Subunits
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Species Specificity
- Transfection
- Ventricular Remodeling