title: Apamin-Sensitive K+ Current Upregulation in Volume-Overload Heart Failure is Associated with the Decreased Interaction of CK2 with SK2.
abstract: Recent studies have shown that the sensitivity of apamin-sensitive K(+) current (I KAS, mediated by apamin-sensitive small conductance calcium-activated potassium channels subunits) to intracellular Ca(2+) is increased in heart failure (HF), leading to I KAS upregulation, action potential duration shortening, early after depolarization, and recurrent spontaneous ventricular fibrillation. We hypothesized that casein kinase 2 (CK2) interacted with small conductance calcium-activated potassium channels (SK) is decreased in HF, and protein phosphatase 2A (PP2A) is increased on the opposite, upregulating the sensitivity of I KAS to intracellular Ca(2+) in HF. Rat model of volume-overload HF was established by an abdominal arteriovenous fistula procedure. The expression of SK channels, PP2A and CK2 was detected by Western blot analysis. Interaction and colocalization of CK2 with SK channel were detected by co-immunoprecipitation analysis and double immunofluorescence staining. In HF rat left ventricle, SK3 was increased by 100 % (P < 0.05), and SK2 was not significantly changed. PP2A protein was increased by 94.7 % in HF rats (P < 0.05), whereas the level of CK2 was almost unchanged. We found that CK2 colocalized with SK2 and SK3 in rat left ventricle. With anti-CK2α antibody, SK2 and SK3 were immunoprecipitated, the level of precipitated SK2 decreased by half, whereas precipitated SK3 was almost unchanged. In conclusion, the increased expression of total PP2A and decreased interaction of CK2 with SK2 may underlie enhanced sensitivity of I KAS to intracellular Ca(2+) in volume-overload HF rat.
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.|Shaanxi Key Laboratory of Molecular Cardiology (Xi'an Jiaotong University), Xi'an, 710061, Shaanxi, China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, 710061, Shaanxi, China.
authors.forename: Tingzhong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Bingxue
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Ning
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Peijing
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China. maaiqun@medmail.com.cn.|Shaanxi Key Laboratory of Molecular Cardiology (Xi'an Jiaotong University), Xi'an, 710061, Shaanxi, China. maaiqun@medmail.com.cn.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, 710061, Shaanxi, China. maaiqun@medmail.com.cn.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Ma
mesh_terms: D000200:Action Potentials; D000818:Animals; D001030:Apamin / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D004195:Disease Models, Animal; D004452:Echocardiography; D000081410:Germinal Center Kinases; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D015854:Up-Regulation; D000099317:Hippo Kinases
chemical_list: D001030:Apamin; D047390:Casein Kinase II; D000081410:Germinal Center Kinases; D011188:Potassium; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases; D051640:Small-Conductance Calcium-Activated Potassium Channels; C481222:Slk protein, rat; D000099317:Hippo Kinases
keywords: Apamin-sensitive K+ current; Heart failure; Protein kinase CK2; Protein phosphatase 2A; SK channels