POTASSIUM CHANNELS ACTIVATED IN THE ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION IN GUINEA-PIG CORONARY-ARTERY

1. Properties of the endothelium-dependent hyperpolarization evoked by acetylcholine (ACh) in smooth muscle of the guinea-pig coronary arter y were investigated using conventional microelectrode techniques. 2. A Ch hyperpolarized the membrane in an endothelium-dependent manner. The hyperpolarization comprised two components: an initial and a slow hyp erpolarization. The former appeared during application of ACh, while t he latter occurred after withdrawal of ACh. 3. Indomethacin and diclof enac, inhibitors of the enzyme cyclo-oxygenase, blocked only the slow hyperpolarization, indicating that this potential was produced by endo thelial prostanoids. 4. Clotrimazole and SKF 525a, known inhibitors of the enzyme cytochrome P450, inhibited both the initial and the slow h yperpolarizations, suggesting that these chemicals acted as non-select ive inhibitors oi. arachidonic acid metabolism, Inhibition of the lipo xygenase pathway of arachidonic acid metabolism by nordihydroguaiareti c acid had no effect on either component of the hyperpolarization. 5. The slow hyperpolarization was inhibited by 4-aminopyridine (4-AP; 10( -4)-10(-3) M) and glibenclamide (10(-6) M). The initial hyperpolarizat ion was greatly inhibited by charybdotoxin (CTX; 5 x 10(-8) M) and par tially inhibited by apamin (10(-7) M), but was not inhibited by gliben clamide (10(-5) M). Ba2+ (10(-4) M) depolarized the membrane and incre ased the amplitude of both components of the ACh-induced hyperpolariza tion. 6. Hyperpolarizations produced by Y-26763, a K+ channel opener, were inhibited by glibenclamide, but not by 4-AP. 7. The results indic ate that the slow hyperpolarization is produced by endothelial prostan oids through activation of 4-AP-sensitive K+ channels (possibly delaye d rectifier type). The initial hyperpolarization is produced mainly th rough activation of CTX-sensitive K+ channels (possibly Ca2+-sensitive type).