Human brain capillary endothelium: modulation of K+ efflux and K+, Ca2+ uptake by endothelin

This report describes K+ efflux, K+ and Ca2+ uptake responses to endothelins (ET-1 and ET-3) in cultured endothelium derived from capillaries of human brain (HBEC). ET-1 dose dependently increased K+ efflux, K+ and Ca2+ uptake in these cells. ET-1 stimulated K+ efflux occurred prior to that of K+ uptake. ET-3 was ineffective. The main contributor to the ET-1 induced K+ uptake was ouabain but not bumetanide-sensitive (Na+-K+-ATPase and Na+-K+-Cl- cotransport activity, respectively). All tested paradigms of ET-1 effects in HBEC were inhibited by selective antagonist of ET(A) but not ET(B) receptors and inhibitors of phospholipase C and receptor-operated Ca2+ channels. Activation of protein kinase C (PKC) decreased whereas inhibition of PKC increased the ET-1 stimulated K+ efflux, K+ and Ca2+ uptake in HBEC. The results indicate that ET-1 affects the HBEC ionic transport systems through activation of ET(A) receptors linked to PLC and modulated by intracellular Ca2+ mobilization and PKC.