"Weak toxin" from Naja kaouthia is a nontoxic antagonist of alpha 7 and muscle-type nicotinic acetylcholine receptors

A novel "weak toxin" (WTX) from Naja kaouthia snake venom competes with [I- 125]alpha -bungarotoxin for binding to the membrane-bound Torpedo californi ca acetylcholine receptor (AChR), with an IC50 of similar to2.2 muM. In thi s respect, it is similar to 300 times less potent than neurotoxin II from N aja oxiana and alpha -cobratoxin from N. kaouthia, representing short-type and long-type alpha -neurotoxins, respectively. WTX and alpha -cobratoxin d isplaced [I-125]alpha -bungarotoxin from the Escherichia coli-expressed fus ion protein containing the rat alpha7 AChR N-terminal domain 1-208 preceded by glutathione S-transferase with IC50 values of 4.3 and 9.1 muM, respecti vely, whereas for neurotoxin II the IC50 value was >100 muM. Micromolar con centrations of WTX inhibited acetylcholine-activated currents in Xenopus oo cyte-expressed rat muscle AChR and human and rat alpha7 AChRs, inhibiting t he latter most efficiently (IC50 of similar to8.3 muM). Thus, a virtually n ontoxic "three-fingered" protein WTX, although differing from alpha -neurot oxins by an additional disulfide in the N-terminal loop, can be classified as a weak alpha -neurotoxin. It differs from the short chain alpha -neuroto xins, which potently block the muscle-type but not the alpha7 AChRs, and is closer to the long alpha -neurotoxins, which have comparable potency again st the above-mentioned AChR types.