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Mitochondrial Calcium Dysregulation during Hypoxic Injury to Cardiac Myocytes

  • Elinor J. Griffiths
Chapter
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Conclusions

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.

Keywords

Mitochondrial Permeability Transition Pore Transport Pathway Mitochondrial Permeability Transition Pore Heart Mitochondrion Mitochondrial Calcium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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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