Neuronal nicotinic acetylcholine receptors are modulated by zinc.
It is known that zinc modulates nicotinic acetylcholine receptors (nAChRs). Here, we studied the effects of zinc on neuronal alpha4beta4 nAChRs, expressed in Xenopus oocytes and activated by nicotine. Membrane ion currents elicited by nicotine (10 nM to 100 microM) were enhanced by zinc (100 microM). Maximal zinc potentiation of the nicotine-activated current (2530%) occurred at 50 nM nicotine, and potentiation gradually decreased as the nicotine concentration increased. The EC(50) and IC(50) for the nicotine-activated current were 639 nM and 14.7 microM nicotine, respectively. Both parameters decreased in the presence of zinc to 160 nM and 4.6 microM, respectively, probably due to an increase of sensitivity of nAChRs for nicotine. We used different concentrations and durations of exposure to nicotine, due to desensitization of nAChRs directly depends on both these factors. With 500 nM nicotine and 20 min washing periods between nicotine applications, zinc potentiation remained constant, 901% for 2 min and 813% for 20 min of nicotine exposure. With continuous application of nicotine, zinc potentiation decreased as the time of nicotine exposure increased, 721% for 2 min and 254% for 48 min of nicotine exposure. Our results indicate that zinc-potentiating effects on alpha4beta4 nAChRs strongly depend on both concentration and time of exposure to nicotine, suggesting that zinc potentiation depends on the degree of desensitization.
Vázquez-Gómez
Elizabeth
E
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla, Querétaro 76230, Mexico.
García-Colunga
Jesús
J
D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014982:Xenopus laevis; D015032:Zinc / Q000502:physiology*; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D017967:Zinc Compounds; C427403:alpha(4)beta(4) nicotinic receptor; D009538:Nicotine; C016837:zinc chloride; D015032:Zinc