Preservation of TSPO by chronic intermittent hypobaric hypoxia confers antiarrhythmic activity

• Published in: Journal of cellular and molecular medicine Vol. 15; no. 1; pp. 134 - 140
• Main Authors: Li, Jun, Xu, Jiahong, Xiao, Junjie, Zhang, Hong, Liang, Dandan, Liu, Yi, Zhang, Yangyang, Liu, Ying, Wen, Wei, Hu, Yaer, Yu, Zhuo, Yan, Biao, Jiang, Bing, Zhou, Zhao‐Nian, Chen, Yi‐Han
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2011; John Wiley & Sons, Inc
• Subjects: Animals; Anti-Arrhythmia Agents - pharmacology; Antiarrhythmics; Arrhythmias, Cardiac - drug therapy; Arrhythmias, Cardiac - metabolism; Arrhythmias, Cardiac - pathology; Blotting, Western; Calcium - metabolism; Cardiac arrhythmia; Cardiovascular disease; Carrier Proteins - metabolism; Chronic Disease; Disease Models, Animal; Experiments; Heart; Homeostasis; Hypoxia; Hypoxia - metabolism; Ischemia; Ischemia - pathology; Ischemia - prevention & control; Laboratory animals; Male; Metabolic rate; Mitochondria; Mitochondria - metabolism; Preservation; Proteins; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Software; ventricular fibrillation; United States > US
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2009.00949.x

Abnormal activation of mitochondrial translocator protein (TSPO) contributes to arrhythmogenesis during cardiac metabolic compromise; however, its role in the antiarrhythmic activities of chronic hypoxia adaptation remains unclear. Our results demonstrated that 80% of normoxic rats developed ischaemic VF, whereas this condition was seldom observed in rats with 14 days of chronic intermittent hypobaric hypoxia (CIHH). TSPO stimulation or inhibition affected the arrhythmias incidence in normoxic rats, but did not change the CIHH‐mediated antiarrhythmic effects. Abrupt and excessive elevation of TSPO activity was positively linked to ischaemic VF, and CIHH preserved TSPO activity during ischaemia. The preservation of TSPO activity by CIHH also contributed to the maintenance of intracellular Ca homeostasis. These results suggest that the blunt sensitivity of TSPO to ischaemic stress may be responsible for the antiarrhythmic effects by CIHH.