Glial membrane potentials and their relationship to [K+]o in man and guinea pig

Abstract

✓ Glial cells were studied in vitro in physiologically viable brain slices prepared from tissues obtained during operations for focal epilepsy and brain tumors. The results from human normal and reactive cerebral cortex and glial tumors were compared with those obtained in guinea pig cortex. The resting membrane potential (RMP) or the relationship of RMP to changes in extracellular potassium concentration ([K+]o) were recorded, and the cell was injected iontophoretically with horseradish peroxidase (HRP) for later visualization and correlation with the physiological data. In normal cortex, the marked cells were protoplasmic astrocytes; in reactive cortex, fibrous astrocytes with abnormal processes predominated. The majority of neoplastic glia resembled the reactive astrocytes, except that they showed a pleomorphism that increased with the degree of malignancy. The mean RMP's of glia from normal human and guinea pig cortex, human reactive cortex, and well differentiated astrocytomas were comparable, about −70 mV. In the less differentiated gliomas, the mean RMP's were lower, with the glioblastoma multiforme having the lowest value, −40 ± 7 mV. When the [K+]o was manipulated over a range of 2 to 40 mM/liter, the mean slope of RMP plotted against [K+]o indicated that normal human and guinea pig glia were exclusively permeable to K+ between [K+]o of 4 to 40 mM/liter. In contrast, the mean slope of reactive glia at these [K+]o's was less, suggesting a permeability to one or more additional ions. Below 4 mM/liter, the slopes of both normal and reactive glia showed changes in RMP smaller than the values expected of cells that are permeable only to K+. Like the reactive glia, the slopes derived for neoplastic cells did not indicate an exclusive permeability to K+, and some cells from the glioblastoma multiforme showed no change in RMP when [K+]o was varied.