Electrophysiological alterations and upregulation of ATP receptors in retinal glial Muller cells from rats infected with the Borna disease virus

Infection with the neurotropic Boma disease virus (BDV) causes an immune-me diated neurological disease in a broad range of species. In addition to enc ephalitis, BDV-infected Lewis rats develop a retinitis histologically chara cterized by the loss of most retinal neurons. By contrast, the dominating r etinal macroglia, the Muller cells, do not degenerate. It is known from sev eral models of neurodegeneration that glial cells may survive but undergo s ignificant alterations of their physiological parameters. This prompted us to study the electrophysiology and ATP-induced changes of intracellular Ca2 +-concentration ([Ca2+](i)) in Muller cells from BDV-infected rat retinae. Freshly isolated cells were used for whole-cell patch-clamp recordings. Whe reas neither zero current potentials nor membrane resistances showed signif icant alterations, the membrane capacitance increased in cells from BDV-inf ected rats during survival times of up to 8 months. This process was accomp anied by a decrease in K+ current densities. Muller cells from BDV-infected rats were characterized by expression of a prominent fast-inactivating A-t ype K+ current which was rarely found in control cells. Moreover, the numbe r of cells displaying Na+ currents was slightly increased after BDV-infecti on. ATP evoked increases in [Ca2+](i) in Muller cells within retinal wholem ounts of both control and BDV-infected animals. However, the number of ATP- responding isolated cells increased from 24% (age-matched controls) to 78% (cells from animals greater than or equal to 18 weeks after infection). We conclude that in BDV-induced retinopathy, reactive rat Muller cells change their physiological parameters but these changes are different from those i n Muller cells during proliferative vitreoretinopathy in man and rabbit. (C ) 2001 Wiley-Liss, Inc.