Cultured microglial cells have a distinct pattern of membrane channels different from peritoneal macrophages

Abstract

Microglia are the source of the resident macrophages of the brain and thus belong to one of the most reactive cell types in cerebral tissue. They are attributed to have an important role in a number of pathological conditions, such as multiple sclerosis, viral infections like AIDS, and in lethal or sublethal injuries of neurons where the blood-brain barrier is left intact (Streit et al., 1988; McGeer et al., 1988; Gendelman et al., 1989). Microglia share a number of macrophage characteristics but so far lack a distinguishing positive marker. In this study it is shown that microglia are distinguished from other macrophages by a unique pattern of ion channels. We compared membrane currents of microglial cells with those from peritoneal macrophages cultured under identical conditions. Although in macrophages a delayed outward K+ current was previously described (Randriamampita and Trautmann, 1987), microglial cells lacked any specific outward current. Instead, these cells were characterized by large inwardly rectifying currents, activated by hyperpolarizing voltage steps. The reversal potential in different K+ gradients and the sensitivity of the current to to Ba2+, TEA, and 4-AP indicates that this current is K+ selective. In single-channel recordings, a 30 pS K+ selective channel similar to the classical inward rectifier K+ channel was observed. Thus, the expression of membrane channels served not only to distinguish microglia from other cells inside and outside the brain, e.g., blood macrophages, but also suggests a unique functional state of this cell population.

Prostaglandin E2 and 4‐Aminopyridine Prevent the Lipopolysaccharide‐Induced Outwardly Rectifying Potassium Current and Interleukin‐1β Production in Cultured Rat Microglia

“…Note that the normal trace (solid circles) is inwardly rectifying, reverses between -80 and -60 mV, and displays only a small outward current even with voltage steps to +40 mV. These data are consistent with previous observations (Kettenmann et al, 1990;Norenberg et al, 1992Norenberg et al, , 1994.…”

“…Following LPS stimulation, microglia are transformed into a reactive state that is characterized electrophysiologically by the expression of the K+ OR (Niirenberg et al, 1992), which is lacking in most nonstimulated microglia (Kettenmann et al, 1990;Banati et al, 1991). The presence of this K+ OR is a robust indicator of the functional state of the cell (Fischer et al, 1995).…”

“…Microglia express an inwardly rectifying K+ current (K+ IR) under most nonstimulated (nonreactive) conditions (Kettenmann et al, 1990;Banati et al, 1991). This current is elicited with hyperpolarizing voltage steps, is K+-selective, displays time-dependent inactivation, is blocked by Ba2+ and Cs + , and is sensitive to tetraethylammonium but not 4-aminopyridine (4-AP) (Kettenmann et al, 1990;Norenberg et al, 1992Norenberg et al, , 1994. Following activation by stimuli such as LPS, microglia also express a large outwardly rectifying K+ current (K + OR) (Norenberg et al, 1992).…”

Effects of ATP and elevated K+ on K+ currents and intracellular Ca2+ in human microglia

“…The latter value is close to the expected reversal potential for inward K ϩ with the solutions employed in these experiments. 17 In the presence of ATP (after 1 min of perfusion; Fig. 4), the slope conductance increased to 5.2 nS and the reversal potential was shifted in a depolarizing direction to Ϫ72 mV.…”

The origin and differentiation of microglial cells during development

“…Second, some markers that label macroglial cells have been reported also to label microglia (Dickson and Mattiace, 1989;Wolswijk, 1995). And third, microglial cells have features di erent from other cells of the mononuclear phagocytic system: they display particular morphological features in vitro (Giulian et al, 1995), proliferate spontaneously in culture (Giulian et al, 1995), and have a distinct ion channel pattern di erent from that of monocytes and macrophages in non-nervous tissues (Kettenmann et al, 1990;Brockhaus et al, 1993).…”