SAPECIN-B, A NOVEL FLY TOXIN, BLOCKS MACROSCOPIC K-LINE( CURRENTS IN THE GH(3) RAT PITUITARY CELL)

Sapecin B is structurally homologous to charybdotoxin (CTX), which is found in scorpion venom. This study investigated the effects of sapeci n B on the Ca2+-activated K+ currents [I-K(Ca)] and the rapidly inacti vating K+ currents in clonal rat GH(3) pituitary cells with whole cell voltage-clamp methods. Sapecin B (20 nM) reversibly blocked the CTX-s ensitive I-K(Ca) (the BK current) in a dose-dependent manner, with a h alf-maximal inhibitory concentration of similar to 0.9 nM, comparable to that of 0.08-0.4 nM for CTX. The Ca2+ currents in GH(3) cells, howe ver, were not affected by sapecin B (40 nM), indicating that the block ade of I-K(Ca) by sapecin B is not a secondary effect of Ca2+ current inhibition. The effect of sapecin B on I-K(Ca) resembled that of CTX, as expected from the structural similarities shared by CTX and sapecin B. We also found that sapecin B largely inhibited the 4-aminopyridine -sensitive, rapidly inactivating K+ currents in a dose-dependent manne r, with a half-maximal inhibitory concentration of similar to 40 nM, w hereas CTX had little effect on this current in GH(3) cells. Sapecin B may thus provide a useful tool, complementary to CTX, for probing the functional role of molecular domains in the BK channels and the struc tural similarities common to the BK and the rapidly inactivating A-typ e K+ channels.