Full activation of an α7-α3β4 nicotinic receptor complex decreases desensitization receptor in human chromaffin cells
Jimenez-Pompa, A.; Sanz-Lazaro, S.; Medina-Polo, J.; Gonzalez-Enguita, C.; Blazquez, J.; McIntosh, J. M.; Albillos, A.
Show abstract
7 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 7 and 3{beta}4 nicotinic receptors physically interact in human chromaffin cells of adrenal glands. The full activation of this 7-3{beta}4 receptor complex avoids subtypes receptor desensitization, leading to gradual increase of currents with successive acetylcholine pulses. Instead, full and partial activation with choline of 7 and 3{beta}4 subtypes, respectively, of this linked receptor leads to 7 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 7-3{beta}4 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.
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