摘要
Nicotine, the major addictive substance in tobacco, interacts with nicotinic acetylcholine receptors (nAChRs) located in neuronal and glial cells, modulating synaptic transmission and memory. Here, we show that nAChRs agonists, including nicotine, acetylcholine, and choline, increase the intracellular Ca2+ concentration ([Ca2+]i) in cultured hippocampal astrocytes, indicating the involvement of nAChRs. Interestingly, inhibition of nAChRs, with a cocktail of antagonists (mecamylamine, methyllycaconitine plus dihydro-β- erythroidine), does not prevent the astrocytic [Ca2+]i increases generated by nicotine. This last effect would be attributable to inhibition of K+ currents by nicotine in these cells, as previously we showed using patch- clamp recordings. Furthermore, the application of tetraethylammonium, an inhibitor of K+ currents, also increases the [Ca2+]i. Together, these results indicate that nicotine increases [Ca2+]i in hippocampal astrocytes through two pathways: by activation of nAChRs, and likely by direct inhibition of K+ currents.
Nicotine, the major addictive substance in tobacco, interacts with nicotinic acetylcholine receptors (nAChRs) located in neuronal and glial cells, modulating synaptic transmission and memory. Here, we show that nAChRs agonists, including nicotine, acetylcholine, and choline, increase the intracellular Ca2+ concentration ([Ca2+]i) in cultured hippocampal astrocytes, indicating the involvement of nAChRs. Interestingly, inhibition of nAChRs, with a cocktail of antagonists (mecamylamine, methyllycaconitine plus dihydro-β- erythroidine), does not prevent the astrocytic [Ca2+]i increases generated by nicotine. This last effect would be attributable to inhibition of K+ currents by nicotine in these cells, as previously we showed using patch- clamp recordings. Furthermore, the application of tetraethylammonium, an inhibitor of K+ currents, also increases the [Ca2+]i. Together, these results indicate that nicotine increases [Ca2+]i in hippocampal astrocytes through two pathways: by activation of nAChRs, and likely by direct inhibition of K+ currents.
