A CHARYBDOTOXIN-SENSITIVE, CA2-ACTIVATED K+ CHANNEL WITH INWARD, RECTIFYING PROPERTIES IN BRAIN MICROVASCULAR ENDOTHELIAL-CELLS - PROPERTIES AND ACTIVATION BY ENDOTHELINS()

A charybdotoxin-sensitive, Ca2+-activated K+ channel was identified in cultured rat brain capillary endothelial cells by using conventional single-channel recording techniques and Rb-86(+)-influx and efflux exp eriments. Channel activity was dependent on the presence of Ca2+ on th e cytosolic face of the membrane with a threshold concentration of 100 nM. It was inhibited by charybdotoxin (IC50 30 nM) and quinine (IC50 0.1 mM)but not by apamin. K(Ca) channels showed unusual inward rectify ing properties under asymmetrical ionic conditions. They were activate d by endothelin-1 (EC(50) 0.7 nM) and endothelin-3 (EC(50) 7-10 nM), T he actions of endothelins were prevented by BQ-123 (K-i = 8 nM) in a c ompetitive fashion, hence suggesting the involvement of an ET(A)-recep tor subtype. The channel activity was unaffected by cyclic AMP- or cyc lic GMP-elevating agents. The possible role of the intermediate conduc tance, Ca2+-activated K+ channels for mediating K+ movements across th e blood-brain barrier is discussed.