Physiology

In order for microglial cells to perform their task of responding to changes in CNS microenvironment, they must be able to sense changes in the extracellular microenvironment. This function can be achieved through the activation of ion channels. To date microglial cells have been shown to possess six types of K+ channel, H+ channel, Na+ channels, Ca2+ channels, Ca2 + -release-activated Ca2+ channels, and voltage-dependent and voltage-independent Cl channels. However, the level of channel expression depends upon the state of the microglia, with activated microglia exhibiting different levels of channel expression than resting microglia. The inward rectifier K+ channels are inhibited by G-protein activation and appear to be involved in regulating membrane potential, but so far no role has been suggested for delayed rectifier channels, although they may be involved in membrane repolarization and cell volume regulation . Both inward and outward rectifier channels are inhibited by increased intracellular Ca2 + , whereas, as expected, an increase in Ca2+ to 1 mM activates the Ca2 + -activated K+ channel. Voltage-gated H+ channels are expressed in phagocytic micro-glia. Their function is thought to be H+ extrusion after phagocytic production of H + . Increases in intracellu-lar H+ (decreased pH) and cell swelling activate this current, suggesting that it acts as a negative feedback mechanism to protect microglia from cytotoxic intra-cellular acidification and acidosis-induced swelling.

Na+ channels are expressed in ramified microglia and have been proposed to play a role in membrane depolarization and regulation of morphological changes, although there is no firm evidence for this. L-type Ca2+ channels are present on microglia and are thought to be the pathway of increased intracellular Ca2+ by PrP and b-amyloid fragments. Capacitative Ca2+ currents were induced in rat microglia being perfused with IP3. However, although their existence has been shown, too little is known about them to compare them to known CRAC channels. However, it has been proposed that they play a part in microglial superoxide production. It is thought that functional Cl_ channels are required for changes in membrane potential and for the induction of microglial ramification, but not for maintenance of the shape. Microglia also contain a host of surface receptors, including AMPA receptors and thrombin receptors, although future research will no doubt uncover more receptor expression on microglia.

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