Mitochondrial Calcium Dysregulation during Hypoxic Injury to Cardiac Myocytes

  • Elinor J. Griffiths


The work discussed above provides evidence that dramatic alterations occur in mitochondrial Ca2+ transport pathways during hypoxia; Ca2+ entry occurs via Na+/Ca2+ exchange (the normal efflux pathway), whereas the Ca2+ uniporter, (the normal influx route) is largely inactive. Clonazepam, but not ruthenium red, provided protection against hypoxia/reoxygenation damage in this model. Clonazepam, however, though a useful tool for studying mitochondrial Ca2+ transport (at least in rat myocytes), cannot be used in whole animals because of its non-myocardial effects, mainly on the nervous system. More specific compounds are clearly needed, especially now it is apparent that Ca2+ transport pathways differ under normoxic and hypoxic conditions. A new ruthenium red derivative has recently been synthesized by Matlib and colleagues (1998), apparently with very few nonspecific effects in myocytes.

One drawback of the work described above is that [Ca2+]m and [Ca2+]c could not be measured in the same cell. Accomplishment of this, together with information regarding the subcellular behavior of individual mitochondria, will provide valuable information on the roles of Ca2+ transport pathways during myocardial injury. Studies using more-specific inhibitors would then determine whether these pathways are primary sites for protective intervention and would answer the question of whether abnormal mitochondrial Ca2+ homeostasis is a leading cause of cell injury or a secondary result.


Mitochondrial Permeability Transition Pore Transport Pathway Mitochondrial Permeability Transition Pore Heart Mitochondrion Mitochondrial Calcium 
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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Elinor J. Griffiths
    • 1
  1. 1.Bristol Heart InstituteUniversity of Bristol, Bristol Royal InfirmaryBristolUK

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