title: Possible pathway of Na(+) flux into mitochondria in ischemic heart.
abstract: Previous studies showed that myocardial Na(+) overload during ischemia directly induced mitochondrial damage. The pathway for Na(+) flux into mitochondria remains unclear. We examined possible routes for Na(+) flux into mitochondria in the ischemic heart. Isolated perfused rat hearts were subjected to 15- to 35-min ischemia followed by 60-min reperfusion and then Na(+) content and respiratory function in mitochondria of the ischemic heart were determined. The mitochondrial Na(+) content of the ischemic heart was ischemic duration-dependently increased, associated with a reduction in mitochondrial respiratory function. To mimic induction of mitochondrial Na(+) overload in vitro, isolated mitochondria were incubated with 6.25 to 50 mM NaCl or sodium lactate, a metabolite of anaerobic glycolysis, in the presence and absence of a mitochondrial Na(+)/Ca(2+) exchanger inhibitor CGP37157 and a monocarboxylate transporter (MCT) inhibitor α-cyano-4-hydroxy cinnamic acid (CHCA). Incubation of mitochondria with NaCl or sodium lactate increased the mitochondrial Na(+) concentration. This increase in mitochondrial Na(+) was partially attenuated by the presence of either inhibitor. Combined treatment of mitochondria with both inhibitors attenuated sodium lactate-induced increase in Na(+) content to a greater degree than that treated with either agent. These results suggest that mitochondrial Na(+)/Ca(2+) exchanger and MCT inhibitor-sensitive Na(+) transporter are possible pathways for the mitochondrial Na(+) overload in the ischemic myocardium.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432–1Horinouchi, Hachioji, Tokyo 192–0392, Japan. tanonaka@toyaku.ac.jp
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tanonaka
authors.forename: Kanataka
authors.initials: K
authors.lastname: Motegi
authors.forename: Toru
authors.initials: T
authors.lastname: Arino
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Marunouchi
authors.forename: Norio
authors.initials: N
authors.lastname: Takagi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeo
mesh_terms: D000818:Animals; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D027501:Monocarboxylic Acid Transporters; D019831:Sodium-Calcium Exchanger; D012964:Sodium