Tissue specific sensitivity of mitochondrial permeability transition pore to Ca2+ ions.
Ca(2+)-induced opening of the mitochondrial permeability transition pore (MPTP) is involved in induction of apoptotic and necrotic processes. We studied sensitivity of MPTP to calcium using the model of Ca(2+)-induced, cyclosporine A-sensitive mitochondrial swelling. Presented data indicate that the extent of mitochondrial swelling (dA520/4 min) induced by addition of 25 microM Ca2+ is seven-fold higher in liver than in heart mitochondria (0.564 +/- 0.08/0.077 +/- 0.01). The extent of swelling induced by 100 microM Ca2+ was in liver tree times higher than in heart mitochondria (0.508 +/- 0.05/ 0.173 +/- 0.02). Cyclosporine A sensitivity showed that opening of the MPTP is involved. We may thus conclude that especially at low Ca2+ concentration heart mitochondria are more resistant to damaging effect of Ca2+ than liver mitochondria. These finding thus support hypothesis that there exist tissue specific strategies of cell protection against induction of the apoptotic and necrotic processes.
Endlicher
René
R
Department of Physiology, Charles University in Prague, Faculty of Medicine and University Hospital Hradec Králové, Czech Republic. endlicherr@lfhk.cuni.cz
Kriváková
Pavla
P
Lotkova
Halka
H
Milerová
Marie
M
Drahota
Zdenek
Z
Cervinková
Zuzana
Z
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine; D002118:Calcium