Amyloid peptide regulates calcium homoeostasis and arrhythmogenesis in pulmonary vein cardiomyocytes

• Main Authors: Hsuan Ming Tsao, Punate Weerateerangkul, Yao Chang Chen, Yu Hsun Kao, Yung Kuo Lin, Jen Hung Huang, Shih Ann Chen, Yi Jen Chen
• Format: Journal
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84860919402&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/51392
• Institution: Chiang Mai University

Background Amyloid peptides modulate cardiac calcium homoeostasis and play an important role in the pathophysiology of atrial fibrillation. Pulmonary veins (PVs) are critical in the genesis of atrial fibrillation and contain abundant amyloid peptides. Therefore, the purpose of this study is to investigate whether amyloid peptides may change the PV electrical activity through regulating calcium homoeostasis. Methods and results The channel and calcium-handling protein expressions, intracellular calcium and ionic currents were studied in isolated rabbit PV cardiomyocytes in the presence and absence (control) of beta-amyloid (Aβ25-35) for 4-6h, using Western blot analysis, indo-1 fluorimetric ratio and whole-cell patch clamp techniques. Aβ25-35decreased the expressions of CaV1.2, total or Ser16-phosphorylated phospholamban (p-PLB), p-PLB/PLB ratio, sodium/calcium exchanger, but did not change ryanodine receptor, sarcoplasmic reticulum (SR) ATPase and K+channel proteins (Kir2.1, Kir2.3, Kv1.4, Kv1.5 and Kv4.2). Aβ25-35-treated cardiomyocytes had smaller calcium transient, SR calcium store, L-type calcium current and sodium/calcium exchanger current than control cardiomyocytes. Moreover, Aβ25-35-treated cardiomyocytes (n=20) had shorter 90% of the action potential duration (82±3 vs. 93±5ms, P<0·05) than control cardiomyocytes (n=16). Conclusion Aβ25-35has direct electrophysiological effects on PV cardiomyocytes. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.