Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at http://www.ucl.ac.uk/finance/research/post_award/post_award_contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Slow calcium waves and redox changes precede mitochondrial permeability transition pore opening in the intact heart during hypoxia and reoxygenation.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Davidson SM, Yellon DM, Murphy MP, Duchen MR
  • Publication date:
  • Pagination:
    445, 453
  • Journal:
    Cardiovasc Res
  • Volume:
  • Issue:
  • Status:
  • Country:
  • PII:
  • Language:
  • Keywords:
    Animals, Calcium Signaling, Cell Death, Hypoxia, Mice, Mitochondrial Membrane Transport Proteins, Mitochondrial Membranes, Mitochondrial Permeability Transition Pore, Myocardial Reperfusion Injury, Myocardium, Myocytes, Cardiac, Oxidation-Reduction, Perfusion, Rats
AIMS: Opening of the mitochondrial permeability transition pore (mPTP) is an important step on the pathway towards cardiomyocyte death, defining the extent of injury following cardiac ischaemia and reperfusion. In isolated mitochondria, mPTP opening is triggered by calcium overload facilitated by oxidative stress. In isolated cells, however, it has been suggested that mPTP opening occurs before calcium overload and is stimulated by oxidative stress. Our objective was to establish the events that cause mPTP opening in the intact heart. METHODS AND RESULTS: We performed multiphoton imaging of Langendorff-perfused mouse hearts expressing an inducible, Ca(2+)-sensitive reporter (circularly Permuted GFP and calmodulin (CaM), version 2), to examine the spatiotemporal relationship between [Ca(2+)](c), redox state, and mPTP opening in the intact heart during hypoxia and reoxygenation at sub-myocyte resolution. We found that during reperfusion, calcium waves propagated across multiple cells at 3.3 µm/s. mPTP opening caused an abrupt loss of mitochondrial membrane potential, measured using a potentiometric dye, which was invariably preceded by a rise in [Ca(2+)](c). The probability that localized [Ca(2+)](c) waves led to mPTP opening was greater early during reoxygenation. During reoxygenation, coordinated redox changes also occurred across large regions and preceded mPTP opening on average by 122 ± 38 s. Fewer [Ca(2+)] waves led to mPTP opening in the presence of mPTP inhibitor cyclosporin A or mitochondrial-targeted scavenger of reactive oxygen species, MitoQ. CONCLUSION: These experiments define the spatiotemporal relationship between changes in [Ca(2+)](c), redox state and mPTP opening during reoxygenation in the intact heart. Tissue oxidation coincident with localized calcium waves together conspire to cause mPTP opening and subsequent cell death.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Pre-clinical & Fundamental Science
Cell & Developmental Biology
Pre-clinical & Fundamental Science
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by