Exercise training induces respiratory substrate-specific decrease in Ca2+-induced permeability transition pore opening in heart mitochondria.
The purpose of this study was to determine whether regular exercise (treadmill running, 10 wk) alters the susceptibility of rat isolated heart mitochondria to Ca(2+)-induced permeability transition pore (PTP) opening and whether this could be associated with changes in the modulation of PTP opening by selected physiological effectors. Basal leak-driven and ADP-stimulated respiration in the presence of substrates for complex I, II, and IV were not affected by training. Fluorimetric studies revealed that in the control and exercise-trained groups, the amount of Ca(2+) required to trigger PTP opening was greater in the presence of complex II vs. I substrates (230 +/- 12 vs. 134 +/- 7 nmol Ca(2+)/mg protein, P < 0.01; pooled average of control and trained groups). In addition, with a substrate feeding the complex II, training increased by 45% (P < 0.01) the amount of Ca(2+) required to trigger PTP opening both in the presence and absence of the PTP inhibitor cyclosporin A. However, membrane potential, reactive oxygen species production, NAD(P)H ratio, and Ca(2+) uptake kinetics were not different in mitochondria from both groups. Together, these results suggest the existence of a substrate-specific regulation of the PTP in heart mitochondria and suggest that regular exercise results in a reduced sensitivity to Ca(2+)-induced PTP opening in presence of complex II substrates.
Marcil
Mariannick
M
Départment de Kinesiology, Université de Montréal, PO Box 6128 Centre-Ville, Montreal, PQ, Canada H3C 3J7.
Bourduas
Karine
K
Ascah
Alexis
A
Burelle
Yan
Y
D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010100:Oxygen / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010809:Physical Fitness / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010100:Oxygen; D002118:Calcium