BLOOD MONOCYTES AND SPLEEN MACROPHAGES DIFFERENTIATE INTO MICROGLIA-LIKE CELLS ON MONOLAYERS OF ASTROCYTES - MEMBRANE CURRENTS

Microglia, the resident macrophages of the central nervous system (CNS), can be distinguished from most other cells of the myelomonocytic lineage by a distinct pattern of membrane currents. In the accompanying paper we have shown that the characteristic morphological feature of microglia, ramification, develops both in microglia and other myelomonocytic cells when they are cocultured with astrocytes. We therefore propose that the electrophysiological properties of microglia also develop under the influence of astrocytes, and, moreover, that these properties can also be induced in other cells of the myelomonocytic lineage. Microglia cultured on poly-d-lysine or on a monolayer of fibroblasts possess an inwardly rectifying K+-current only, which is of composite nature. In single-channel recordings two types of K+-channels are found: i) a noninactivating channel with a conductance of 43pS, and ii) an inactivating channel with 32pS. Microglia cultured on a monolayer of astrocytes additionally develop an outward K+-current and a Na+-current. The electric parameters of activation and inactivation of the microglial Na+-current are identical to those of the neuronal Na+-current. Monocytes from peripheral blood and macrophages from spleen exhibit no inward currents. However, when these cells are cocultured with astrocytes they develop microglia-like membrane currents, including the inward and outward K+-rectifyer and the Na+-current. By contrast, on fibroblasts they retain their macrophage current profile. The expression of the microglia-like membrane currents in the mononuclear phagocytes is induced by a diffusible factor released from the astrocytes into the culture medium, since monocytes and microglia develop the mature microglial current profile, when cultured in astrocyte conditioned medium. These findings show that the current profile of microglia develops only, when they are in association with astrocytes, and that it is induced in myelomonocytic cells from blood and spleen when these also are associated with astrocytes. These findings add to the growing body of evidence that microglia are derived from the myelomonocytic lineage and indicate that the astrocytes are involved in regulating their morphological and functional properties. (C) 1994 Wiley-Liss, Inc.