Abstract
Background-Chronic kidney disease (CKD) increases the occurrence of atrial fibrillation and pulmonary vein (PV) arrhythmogenesis. Calcium dysregulation and reactive oxygen species (ROS) enhance PV arrhythmogenic activity. The purposes of this study were to investigate whether CKD modulates PV electrical activity through dysregulation of calcium homeostasis and ROS. Methods and Results-Biochemical and electrocardiographic studies were conducted in rabbits with and without CKD (induced by 150 mg/kg per day neomycin sulfate and 500 mg/kg per day cefazolin). Confocal microscopy with fluorescence and a whole-cell patch clamp were applied to study calcium homeostasis and electrical activities in control and CKD isolated single PV cardiomyocytes with or without treatment with H89 (1 μmol/L, a protein kinase A inhibitor) and MPG (N-[2-mercaptopropionyl] glycine; 100 μmol/L, a ROS scavenger). The ROS in mitochondria and cytosol were evaluated via intracellular dye fluorescence and lipid peroxidation. CKD rabbits had excessive atrial premature captures over those of control rabbits. Compared with the control, CKD PV cardiomyocytes had a faster beating rate and larger calcium transient amplitudes, sarcoplasmic reticulum calcium contents, sodium/calcium exchanger currents, and late sodium currents but smaller L-type calcium current densities. CKD PV cardiomyocytes had a higher frequency and longer duration of calcium sparks and more ROS in the mitochondria and cytosol than did controls. Moreover, H89 suppressed all calcium sparks in CKD PV cardiomyocytes, and H89- and MPG-treated CKD PV cardiomyocytes had similar calcium transients compared with control PV cardiomyocytes. Conclusions-CKD increases PV arrhythmogenesis with enhanced calcium-handling abnormalities through activation of protein kinase A and ROS.
Original language | English |
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Article number | e005701 |
Journal | Journal of the American Heart Association |
Volume | 6 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jul 1 2017 |
Keywords
- Atrial fibrillation
- Calcium regulation
- Chronic kidney disease
- Pulmonary vein
- Reactive oxygen species
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine