title: gp120-induced alterations of human astrocyte function: Na(+)/H(+) exchange, K(+) conductance, and glutamate flux.
abstract: Many human immunodeficiency virus (HIV)-infected patients suffer from impaired neurological function and dementia. This facet of the disease has been termed acquired immunodeficiency syndrome (AIDS)-associated dementia complex (ADC). Several cell types, including astrocytes and neurons, are not productively infected by virus but are involved in ADC pathophysiology. Previous studies of rat astrocytes showed that an HIV coat protein (gp120) accelerated astrocyte Na(+)/H(+) exchange and that the resultant intracellular alkalinization activated a pH-sensitive K(+) conductance. The present experiments were conducted to determine whether gp120 affected human astrocytes in the same fashion. It was found that primary human astrocytes express a pH-sensitive K(+) conductance that was activated on intracellular alkalinization. Also, gp120 treatment of whole cell clamped human astrocytes activated this conductance specifically. Furthermore, gp120 inhibited glutamate uptake by primary human astrocytes. These altered physiological processes could contribute to pathophysiological changes in HIV-infected brains. Because the gp120-induced cell physiological changes were partially inhibited by dimethylamiloride (an inhibitor of Na(+)/H(+) exchange), our findings suggest that modification of human astrocyte Na(+)/H(+) exchange activity may provide a means of addressing some of the neurological complications of HIV infection.
authors.affiliation: Department of Physiology & Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Patton
authors.forename: Z H
authors.initials: ZH
authors.lastname: Zhou
authors.forename: J K
authors.initials: JK
authors.lastname: Bubien
authors.forename: E N
authors.initials: EN
authors.lastname: Benveniste
authors.forename: D J
authors.initials: DJ
authors.lastname: Benos
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004553:Electric Conductivity; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006801:Humans; D011188:Potassium / Q000037:antagonists & inhibitors / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
chemical_list: D015699:HIV Envelope Protein gp120; D020033:Protein Isoforms; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D018698:Glutamic Acid; D000584:Amiloride; D012964:Sodium; D011188:Potassium