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bioRxiv · 10.1101/2020.11.11.360537

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.
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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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Jimenez-Pompa, A., Sanz-Lazaro, S., Medina-Polo, J., Gonzalez-Enguita, C., Blazquez, J., McIntosh, J. M., Albillos, A.. 2020-11-12. Full activation of an α7-α3β4 nicotinic receptor complex decreases desensitization receptor in human chromaffin cells. https://doi.org/10.1101/2020.11.11.360537

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