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.
Department of Physiology, Charles University in Prague, Faculty of Medicine and University Hospital Hradec Králové, Czech Republic. endlicherr@lfhk.cuni.cz
René
R
Endlicher
Pavla
P
Kriváková
Halka
H
Lotkova
Marie
M
Milerová
Zdenek
Z
Drahota
Zuzana
Z
Cervinková
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