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

Many human immunodeficiency virus(HIV)-infected patients suffer from impaired neurological function anddementia. This facet of the disease has been termed acquiredimmunodeficiency syndrome (AIDS)-associated dementia complex (ADC).Several cell types, including astrocytes and neurons, are notproductively 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⁺ exchangeand that the resultant intracellular alkalinization activated apH-sensitive K⁺ conductance. The present experiments wereconducted to determine whether gp120 affected human astrocytes in thesame fashion. It was found that primary human astrocytes express apH-sensitive K⁺ conductance that was activated onintracellular alkalinization. Also, gp120 treatment of whole cellclamped human astrocytes activated this conductance specifically.Furthermore, gp120 inhibited glutamate uptake by primary humanastrocytes. These altered physiological processes could contribute topathophysiological changes in HIV-infected brains. Because thegp120-induced cell physiological changes were partially inhibited bydimethylamiloride (an inhibitor of Na⁺/H⁺exchange), our findings suggest that modification of human astrocyte Na⁺/H⁺ exchange activity may provide a means ofaddressing some of the neurological complications of HIV infection.