MUSCLE-TYPE NICOTINIC ACETYLCHOLINE-RECEPTOR DELTA-SUBUNIT DETERMINESSENSITIVITY TO NONCOMPETITIVE INHIBITORS, WHILE GAMMA-SUBUNIT REGULATES DIVALENT PERMEABILITY

Heterologous expression of nicotinic acetylcholine receptor (nAChR) RN As in Xenopus oocytes was used to examine the structural basis for pha rmacological and physiological differences between muscle-type and neu ronal nAChRs. Neuronal nAChRs have a higher permeability to calcium th an muscle-type nAChRs and display inward rectification, while muscle-t ype nAChRs have a linear current-voltage relation. In addition, neuron al nAChRs are more sensitive to inhibition by a class of compounds kno wn as ''ganglionic blockers''. It has been shown previously that neuro nal-muscle hybrid receptors show increased sensitivity to the use-depe ndent inhibitor of neuronal nAChRs, BTMPS, based on the presence of a neuronal beta subunit. In this study, we report that omission of gamma subunit RNA has a similar effect. alpha beta delta receptors exhibit prolonged inhibition by BTMPS, show a significant permeability to diva lent ions, display inward rectification and are more sensitive to meca mylamine. However, while pharmacological effects are associated with t he presence of an additional delta subunit, the physiological changes described seem to be associated with the presence or absence of a gamm a subunit. These results suggest that, for nAChRs, as is also the case for non-NMDA ionotropic glutamate receptors, the crucial functional p roperty of limiting calcium permeability can be served by a single sub unit. Copyright (C) 1996 Elsevier Science Ltd.