Ion transporters and ischemic mitochondrial dysfunction.
Ischemia-induced ionic imbalance leads to the activation of numerous events including mitochondrial dysfunction and eventual cell death. Dysregulation of mitochondrial Ca(2+) (Ca(2+)(m)) plays a critical role in cell damage under pathological conditions including traumatic brain injury and stroke. High Ca(2+)(m) levels can induce the persistent opening of the mitochondrial permeability transition pore and trigger mitochondrial membrane depolarization, Ca(2+) release, cessation of oxidative phosphorylation, matrix swelling and eventually outer membrane rupture with release of cytochrome c and other apoptogenic proteins. Thus, the dysregulation of mitochondrial Ca(2+) homeostasis is now recognized to play a crucial role in triggering mitochondrial dysfunction and subsequent apoptosis. Recent studies show that some secondary active transport proteins, such as Na(+)-dependent chloride transporter and Na(+)/Ca(2+) exchanger, contribute to ischemia-induced dissipation of ion homeostasis including Ca(2+)(m).
Liu
Yan
Y
Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
Liu
Xiang-jun
XJ
Sun
Dandan
D
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*
D026901:Membrane Transport Proteins; D002118:Calcium