Full activation of an α7-α3β4 nicotinic receptor complex avoids receptor desensitization in human chromaffin cells

Abstract

Abstractα7 nicotinic receptors have been involved in numerous pathologies. A hallmark of these receptors is their extremely fast desensitization, a process not fully understood yet. Here we show that human native α7 and α3β4 nicotinic receptors physically interact in human chromaffin cells of adrenal glands. The full activation of this α7-α3β4 receptor complex avoids subtypes receptor desensitization, leading to gradual increase of currents with successive acetylcholine pulses. Instead, full and partial activation with choline of α7 and α3β4 subtypes, respectively, of this linked receptor leads to α7 receptor desensitization. Therefore choline, a product of the acetylcholine hydrolysis, acts as a brake by limiting the increase of currents by acetylcholine. Very importantly, the efficiency of the α7-α3β4 interaction diminishes in subjets older than 50 years, accordingly increasing receptor desensitization and decreasing nicotinic currents. These results open a new line of research to achieve improved therapeutic treatments for nicotinic receptors related diseases.