Preservation of TSPO by chronic intermittent hypobaric hypoxia confers antiarrhythmic activity.
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.
Key Laboratory of Arrhythmias, Ministry of Education of China, Shanghai, China.
Jun
J
Li
Jiahong
J
Xu
Junjie
J
Xiao
Hong
H
Zhang
Dandan
D
Liang
Yi
Y
Liu
Yangyang
Y
Zhang
Ying
Y
Liu
Wei
W
Wen
Yaer
Y
Hu
Zhuo
Z
Yu
Biao
B
Yan
Bing
B
Jiang
Zhao-Nian
ZN
Zhou
Yi-Han
YH
Chen
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism*; D007511:Ischemia / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000889:Anti-Arrhythmia Agents; D002352:Carrier Proteins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D002118:Calcium