title: Role of membrane ion transport proteins in cerebral ischemic damage.
abstract: Loss of ion homeostasis plays a central role in pathogenesis of ischemic cell damage. Ischemia-induced perturbation of ion homeostasis leads to intracellular accumulation of Ca2+ and Na+ and subsequent activation of proteases, phospholipases, and formation of oxygen and nitrogen free radicals. This signal transduction cascade results in long-term functional and structural changes in membrane and cytoskeletal integrity and eventual cell death. Both ion conductances and ion transporters could affect ion homeostasis. Considerable research effort has been centered on roles of passive fluxes via cation and anion conductances in cerebral ischemic damage. This review will instead focus on the recent studies into the role of secondary active transport proteins in ischemia-induced dissipation of ion homeostasis. Secondary active ion transport proteins are a membrane protein-mediated solute transport mechanism that derives its energy from the combined chemical gradients of the transported ions. They are important in maintaining steady-state intracellular ion concentrations. These include Na+-dependent chloride transport (NKCC), Na+/H+ exchange (NHE), and Na+/Ca2+ exchange (NCX). Results from both in vitro and in vivo experimental studies suggest that these ion transport proteins are potential targets to reduce or prevent ischemia-mediated loss of ion homeostasis.
authors.affiliation: Dept. of Neurosurgery, Univ. of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kintner
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000209:etiology*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology*; D064506:Solute Carrier Family 12, Member 2
chemical_list: D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2