CONTRIBUTIONS OF THE GAMMA AND EPSILON-SUBUNIT FAMILY TO NICOTINIC ACETYLCHOLINE-RECEPTOR FUNCTION

Hybrid acetylcholine (ACh) receptors expressed in Xenopus oocytes were used to study the role of the gamma/epsilon subunit family in determi ning channel function. The receptors were composed of either a mouse g amma, Torpedo gamma, Xenopus gamma or mouse epsilon subunit in combina tion with mouse alpha, beta and delta subunits. The effects of differe nt gamma and epsilon subunits on channel conductance and open time wer e paralleled by their structural relatedness. Of the four subunits stu died, mouse gamma and mouse epsilon are the most divergent in structur e and the receptors containing these subunits were also the most diver gent in function. Torpedo and Xenopus gamma subunits have structural f eatures intermediate to both mouse epsilon and gamma and corresponding ly imparted intermediate functional properties. Of particular interest , ACh receptors formed in combination with a Torpedo gamma subunit had a significantly lower conductance than those containing a mouse epsil on subunit, despite the presence of identical amino acids in all charg e positions previously shown to affect conductance.