FUNCTIONAL-CHARACTERIZATION OF MONGOOSE NICOTINIC ACETYLCHOLINE-RECEPTOR ALPHA-SUBUNIT - RESISTANCE TO ALPHA-BUNGAROTOXIN AND HIGH-SENSITIVITY

The mongoose is resistant to snake neurotoxins, The mongoose muscle ni cotinic acetylcholine receptor (AChR) alpha-subunit contains a number of mutations in the ligand-binding domain and exhibits poor binding of alpha-bungarotoxin (alpha-BTX). We characterized the functional prope rties of a hybrid (alpha-mongoose/beta gamma delta-rat) AChR, Hybrid A ChRs, expressed in Xenopus oocytes, respond to acetylcholine with depo larizing current, the mean maximal amplitude of which was greater than that mediated by the rat AChR, The IC50 of alpha-BTX to the hybrid AC hR was 200-fold greater than that of the rat, suggesting much lower af finity for the toxin, Hybrid AChRs exhibited an apparent higher rate o f desensitization and higher affinity for ACh (EC50 1.3 vs, 23.3 mu M for the rat AChR), Hence, changes in the ligand-binding domain of AChR not only affect the binding properties of the receptor, but also resu lt in marked changes in the characteristics of the current. (C) 1998 F ederation of European Biochemical Societies.