Preservation of TSPO by chronic intermittent hypobaric hypoxia confers antiarrhythmic activity

J Cell Mol Med. 2011 Jan;15(1):134-40. doi: 10.1111/j.1582-4934.2009.00949.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / metabolism*
  • Arrhythmias, Cardiac / pathology
  • Blotting, Western
  • Calcium / metabolism
  • Carrier Proteins / metabolism*
  • Chronic Disease
  • Disease Models, Animal
  • Hypoxia / metabolism*
  • Ischemia / pathology
  • Ischemia / prevention & control*
  • Male
  • Mitochondria / metabolism*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Anti-Arrhythmia Agents
  • Carrier Proteins
  • RNA, Messenger
  • Receptors, GABA-A
  • Tspo protein, rat
  • Calcium