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: Dandan Yang, Tingzhong Wang, Yajuan Ni, Bingxue Song, Feifei Ning, Peijing Hu, Ling Luo, Ya Wang, Aiqun Ma
• Journal: The Journal of membrane biology (J Membr Biol) Vol. 248 Issue 6 Pg. 1181-9 (Dec 2015) ISSN: 1432-1424 [Electronic] United States
• PMID: 26362340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Germinal Center Kinases
• Small-Conductance Calcium-Activated Potassium Channels
• Apamin
• Slk protein, rat
• Casein Kinase II
• Protein Serine-Threonine Kinases
• Protein Phosphatase 2
• Potassium

Topics

• Action Potentials
• Animals
• Apamin (metabolism)
• Casein Kinase II (metabolism)
• Disease Models, Animal
• Echocardiography
• Germinal Center Kinases
• Heart Failure (diagnosis, etiology, metabolism, physiopathology)
• Male
• Myocytes, Cardiac (metabolism)
• Potassium (metabolism)
• Protein Binding
• Protein Phosphatase 2 (metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Protein Transport
• Rats
• Small-Conductance Calcium-Activated Potassium Channels (metabolism)
• Up-Regulation