Abstracts

Two distinct types of the astrocytes have recently been described: electrophysiologically passive, glutamate transporter expressing [quot]GluT[quot] cells and electrophysiologically complex, AMPA glutamate receptor expressing [quot]GluR[quot] cells. Passive protoplasmic astrocytes predominate in mature hippocampus and neocortex. A reduction of the inward rectifier potassium current (Kir) has been observed in astrocytes in experimental and human epilepsies. However, the relationship of this and other alterations in [quot]scar[quot] astrocytes in areas of gliosis to the above classification is not clear., Immunohistochmical and electrophysiological methods were used to examine the functional properties of [quot]scar[quot] astrocytes in areas of gliosis and neuronal cell loss in resected MTLE human hippocampus. Scar astrocytes were compared to astrocytes in non-sclerotic hippocampus and neocortex., Scar astrocytes in the sclerotic hippocampal CA1 area have clear pathological alterations including marked enhancement of GFAP expression and reduction of coupling to surrounding cells. In comparison to nonsclerotic hippocampal and neocortical passive [quot]gluT[quot] astrocytes, scar astrocytes retain some electrophysiological features including low input membrane resistance (49.7[plusmn]16.9 M[Omega], n=5) and linear (passive) current properties. However, scar astrocytes have a significantly depolarized resting membrane potential compared with control (-43.9 [plusmn]7.3 vs -81.8[plusmn]3 mV). This smaller electrical gradient provides a weaker driving force for buffering excessive extracellular glutamate and potassium. In addition, scar passive astrocytes have a dramatic decrease in glutamate transporter current expression. With only a small decrease in total cell current, scar astrocytes retain a large amount of voltage-independent passive current. All electrophysiologically complex cells recorded in sclerotic and nonsclerotic human tissue express NG2 antigen. In comparison to the low level of Cs-sensitive Kir found in control or sclerotic passive astrocytes, a muhc higher level of Kir current was detected in NG2 cells., Our results support the following findings: 1) passive [quot]gluT[quot] scar astrocytes have alterations that impair glutamate transport and potassium clearance in the gliotic hippocampus; 2) in the human brain, complex [quot]gluR[quot] cells express NG2 and may belong to the oligodendrocyte rather than the astrocyte lineage; 3) [quot]GluT[quot] cells do not convert into or become replaced by [quot]gluR[quot] cells in the human epileptic hippocampus., (Supported by NIH R21, K08; Parents Against Childhood Epilepsy.)