gp120-induced alterations of human astrocyte function: Na+/H+ exchange, K+conductance, and glutamate flux

Many human immunodeficiency virus (HIV)-infected patients suffer from impai red neurological function and dementia. This facet of the disease has been termed acquired immunodeficiency syndrome (AIDS)-associated dementia comple x (ADC). Several cell types, including astrocytes and neurons, are not prod uctively infected by virus but are involved in ADC pathophysiology. Previou s studies of rat astrocytes showed that an HIV coat protein (gp120) acceler ated astrocyte Na+/H+ exchange and that the resultant intracellular alkalin ization activated a pH-sensitive K+ conductance. The present experiments we re conducted to determine whether gp120 affected human astrocytes in the sa me fashion. It was found that primary human astrocytes express a pH-sensiti ve K+ conductance that was activated on intracellular alkalinization. Also, gp120 treatment of whole cell clamped human astrocytes activated this cond uctance specifically. Furthermore, gp120 inhibited glutamate uptake by prim ary human astrocytes. These altered physiological processes could contribut e to pathophysiological changes in HIV-infected brains. Because the gp120-i nduced cell physiological changes were partially inhibited by dimethylamilo ride (an inhibitor of Na+/H+ exchange), our findings suggest that modificat ion of human astrocyte Na+/H+ exchange activity may provide a means of addr essing some of the neurological complications of HIV infection.