title: Spinal cord mitochondria display lower calcium retention capacity compared with brain mitochondria without inherent differences in sensitivity to cyclophilin D inhibition.
abstract: The mitochondrial permeability transition (mPT) is a potential pathogenic mechanism in neurodegeneration. Varying sensitivity to calcium-induced mPT has been demonstrated for regions within the CNS possibly correlating with vulnerability following insults. The spinal cord is selectively vulnerable in e.g. amyotrophic lateral sclerosis and increased mPT sensitivity of mitochondria derived from the spinal cord has previously been demonstrated. In this study, we introduce whole-body hypothermia prior to removal of CNS tissue to minimize the effects of differential tissue extraction prior to isolation of spinal cord and cortical brain mitochondria. Spinal cord mitochondria were able to retain considerably less calcium when administered as continuous infusion, which was not related to a general increased sensitivity of the mPT to calcium, its desensitization to calcium by the cyclophilin D inhibitor cyclosporin-A, or to differences in respiratory parameters. Spinal cord mitochondria maintained a higher concentration of extramitochondrial calcium during infusion than brain mitochondria possibly related to an increased set-point concentration for calcium uptake. A hampered transport and retention capacity of calcium may translate into an increased susceptibility of the spinal cord to neurodegenerative processes involving calcium-mediated damage.
authors.affiliation: Department of Anesthesiology, Tokyo Medical University Hachioji Medical Center, Tatemachi, Hachioji, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Morota
authors.forename: Magnus J
authors.initials: MJ
authors.lastname: Hansson
authors.forename: Nagao
authors.initials: N
authors.lastname: Ishii
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kudo
authors.forename: Eskil
authors.initials: E
authors.lastname: Elmér
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchino
mesh_terms: D000408:Alamethicin / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000494:pharmacology*; D007036:Hypothermia, Induced / Q000379:methods; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D007476:Ionophores; D000408:Alamethicin; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D021983:Cyclophilins; D002118:Calcium