Native α6β4* nicotinic receptors control exocytosis in human chromaffin cells of the adrenal gland.

Alberto Pérez-Alvarez, Alicia Hernández-Vivanco, J Michael McIntosh, Almudena Albillos

Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, Madrid, Spain. a.perez@uam.es

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2012 Jan

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In the present study, we have electrophysiologically characterized native nicotinic acetylcholine receptors (nAChRs) in human chromaffin cells of the adrenal gland as well as their contribution to the exocytotic process. α-Conotoxin AuIB blocked by 14 ± 1% the acetylcholine (ACh)-induced nicotinic current. α-Conotoxin MII (α-Ctx MII) exhibited an almost full blockade of the nicotinic current at nanomolar concentrations (IC(50)=21.6 nM). The α6*-preferring α-Ctx MII mutant analogs, α-Ctx MII[H9A,L15A] and α-Ctx MII[S4A,E11A,L15A], blocked nAChR currents with an IC(50) of 217.8 and 33 nM, respectively. These data reveal that nAChRs in these cells include the α6* subtype. The washout of the blockade exerted by α-conotoxin BuIA (α-Ctx BuIA; 1 μM) on ACh-evoked currents was slight and slow, arguing in favor of the presence of a β4 subunit in the nAChR composition. Exocytosis was almost fully blocked by 1 μM α-Ctx MII, its mutant analogs, or α-Ctx BuIA. Finally, the fluorescent analog Alexa Fluor 546-BuIA showed distinct staining in these cells. Our results reveal that α6β4* nAChRs are expressed and contribute to exocytosis in human chromaffin cells of the adrenal gland, the main source of adrenaline under stressful situations.

Citation

Alberto Pérez-Alvarez, Alicia Hernández-Vivanco, J Michael McIntosh, Almudena Albillos. Native α6β4* nicotinic receptors control exocytosis in human chromaffin cells of the adrenal gland. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2012 Jan;26(1):346-54