MODULATION OF POTASSIUM CURRENTS IN CULTURED MURINE MICROGLIAL CELLS BY RECEPTOR ACTIVATION AND INTRACELLULAR PATHWAYS

The electrophysiological properties of ameboid microglia from rodent b rain are dominated by inwardly rectifying potassium channels and by th e lack of outward currents. This channel pattern results in a distinct physiological behavior: depolarizing events, e.g. following adenosine triphosphate receptor activation, can lead to a long lasting membrane depolarization. Here we address the question whether this resting Kchannel activity can be modulated. Intracellular application of guanos ine 5'-O-(3-thiotriphosphate) induced an outward current and led to a complete disappearance of the inward current inward rectifier potassiu m current as measured with the patch clamp technique. Moreover, an ele vation in cytosolic calcium concentration (to 1.6 mu M) via intracellu lar perfusion reversibly blocked the inward current. The inhibition of inward currents by guanosine 5'-O-(3-thiotriphosphate) could be enhan ced by additional adenosine triphosphate receptor activation. Adenosin e triphosphate or tumor necrosis factor receptor activation alone coul d lead to a transient partial block of the inward rectifier and to the transient appearance of a delayed outward current. We conclude that t he activity of the microglia K+ channels and thus the physiological be havior of microglia can be modulated on a time scale or seconds by rec eptor activation and distinct intracellular pathways.