M-TYPE K-EUPEUS( CURRENT INHIBITION BY A TOXIN FROM THE SCORPION BUTHUS)

A number of invertebrate venoms have been tested for effects on M-type K+ currents (I-K(M)) in differentiated mouse neuroblastoma x rat glio ma NG108-15 cells. Among the venoms tested, Buthus eupeus scorpion ven om reversibly inhibited I-K(M) by similar to 44% at 50 mu g/ml. Inhibi tion was not due to activation of bradykinin or nucleotide (pyrymidine ) receptors. On venom fractionation, a polypeptide of 4 kDa was purifi ed that inhibited I-K(M) by similar to 45% with an IC50 of similar to 33 nM. Neither the crude venom nor the purified polypeptide affected t he Ca2+ current or the delayed rectifier K+ current. While the crude v enom prolonged the Na+ current, the polypeptide did not. Thus, the 4 k Da Buthus eupeus polypeptide appears to be a selective inhibitor of I- K(M) in NG108-15 cells.