Volume regulation and metabolism of suspended C6 glioma cells: an in vitro model to study cytotoxic brain edema

Abstract

The in vitro model presented provides an approach to study the nature of cell volume control as well as of swelling mechanisms under pathophysiological conditions. Pertinent parameters of cell volume control can be analyzed in isolation due to a virtually infinite extracellular environment precluding secondary effects of the suspended cells. Exposure of C6 glial cells to hypotonic medium was investigated as a model to study fundamental aspects of cell volume control. In confirmation of studies on other cell types glial cells suspended in hypotonic medium recover cell volume after transient swelling. Normalization of cell volume is associated with stimulation of respiration. Moreover, normalization of cell volume in hypotonic medium can be pharmacologically influenced. Addition of naftidrofuryl which enhances cellular O2-consumption led to acceleration of cell volume recovery. On the other hand, inhibition of Na+-K+-ATPase by ouabain did not prevent regulatory volume decrease ruling out a major role of the Na+-transport enzyme in this process. Contrary to hypotonic suspension, hypertonic exposure did not result in volume regulation during an observation period of 3 h. However, this may not necessarily exclude a capability of cell volume to normalize in hypertonic conditions as observed in vivo. Volume control of glial cells in abnormal osmotic medium may--on a cellular basis--reflect fundamental adaptive processes of central nervous tissue. Knowledge of the physiological and biochemical basis of cell volume control is not only of scientific interest but also of therapeutical significance in patients suffering from cytotoxic brain edema.