M-type K+ current inhibition by a toxin fron the scorpion Buthus eupeus

A number of invertebrate venoms have been tested for effects on M-type K+ currents (IK(M)) in differentiated mouse neuroblastoma X rat glioma NG108-15 cells. Among the venoms tested, Buthus eupeus scorpion venom reversibly inhibited IK(M) by approximately 44% at 50 microgram/ml. Inhibition was not due to activation of bradykinin or nucleotide (pyrimidine) receptors. On venom fractionation, a polypeptide of 4 kDa was purified that inhibited IK(M) by approximately 45% with an IC50 of approximately 33 nM. Neither the crude venom nor the purified polypeptide affected the Ca2+ current or the delayed rectifier K+ current. While the crude venom prolonged the Na+ current, the polypeptide did not. Thus, the 4 kDa Buthus eupeus polypeptide appears to be a selective inhibitor of IK(M) in NG108-15 cells.