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RESEARCH PRODUCT

Chapter 6: Swelling of C6 glioma cells and astrocytes from glutamate, high K+ concentrations or acidosis

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Publisher Summary With impaired energy supply, cell swelling results from the failure of Na+/K+-ATPase according to the pump-leak model of cell volume regulation. In a series of in vitro studies, glial cell volume changes during defined and strictly controlled alterations of the extracellular environment in vitro. Experiments were performed with C6 glioma cells and astrocytes from primary culture. The major advantages of using C6 cells are the rapid availability of large cell numbers necessary for reliable flow cytometric volume measurements, and the homogeneous cell size distribution permitting the detection of even subtle volume changes. The sodium-potassium pump was blocked by the cardiac glycoside ouabain. The Na+ gradient was lost by this treatment within 90 min in C6 cells. Glutamate is an excitatory transmitter in the CNS. The uptake of glutamate together with sodium ions by glial elements resulted in an increase of cellular volume and proposed as one of the mechanisms causing the formation of cytotoxic edema in ischemic and postischemic brain. Lactacidosis from anaerobic metabolism is a consequence of cerebral ischemia, seizures and head injury. Using the in vitro system, the swelling-inducing capacity of extracellular lactacidosis was confirmed.