Chloride Channels and Carriers in Cultured Glial Cells

Abstract

Since their discovery, glial cells have generally been considered to be passive elements with only a few of their properties being recognized as of great importance for the proper functioning of the nervous system, e.g., the formation of myelin by oligodendrocytes and Schwann cells (for reviews see Morell and Norton, 1980), the clearance of K + from the extracellular space by astrocytes (Orkand, 1977, 1980), the guidance of neurons during development (Rakic, 1981), and the uptake of neurotransmitters (Hertz, 1979). Neurons and glial cells are separated by the extracellular space and communication between these two cell populations requires that signals travel across the space. Release of K + into the extracellular space during neuronal activity and the response of glial cells, which take up the excess K + to regulate extracellular concentrations, is an example of such a signal between neurons and glial cells (e.g., Salem et al., 1975; Sykova and Orkand, 1980; Walz and Hertz, 1983b). The potassium uptake by glial cells is mediated by passive processes, namely spatial buffering and passive KC1 uptake, and/or by stimulation of the Na +/K + -ATPase (Kettenmann, 1987a). The efficiency of spatial buffering seems to be determined by the density and distribution of K + channels (Newman, 1985a,b, 1986; Orkand, 1977), that of KCl uptake by the relative density of K + and Cl− channels (Ballanyi et al., 1986; Kettenmann, 1987b). Thus, expression of Cl− channels in glia can play a functional role in K + homeostasis. Recent observations indicate that not only K + undergoes changes in the extracellular space during neuronal activity, but also Na +, Ca24, H +, and Cl−(Chesler, 1987; Dietzel et al., 1982; Nicholson, 1980a,b). Thus, glial cells may be involved in controlling the free concentration of other physiologically relevant ions including H + and Cl. This would not be surprising, since most ion transport systems across cell membranes function as co- or countertransporters. A well-known example is the countertransport of Na + and K + by the Na + /K + -ATPase, which is present in glial cells (Orkand, 1977). Other transport systems present in glial cells include Na +/H + and Cl−/HCO− 3 exchangers, Na +/HCO− 3 and K +/CI− cotransporters (Hoppe and Kettenmann, 1989a; Kettenmann and Schlue, 1988; Kimelberg et al.,1979). The combined activity of these carriers and the Na +, K +, Cl−, and HCO− 3 channels which can be expressed by glial cells (Bevan et al., 1986; Gray et al., 1986; Kettenmann, 1987b; Astion et al., 1987; Tang et al., 1979) are likely to strongly influence nervous tissue extracellular ionic microenvironment.