Cardiac effects of nicotine exposure in Drosophila melanogaster are mediated by subunits α1 and 7 of the nicotine receptor

SANTALLA, MANUELA; PAGOLA, LUCIA; GÓMEZ, IVANA; BALCAZAR, DARÍO; VALVERDE CARLOS; FERRERO, PAOLA

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Congreso; Sociedad Argentina de Fisiología; 2020

Therelationship between substances consumed by humans and their impact on healthhas been explored in different animal models in an attempt to deepen onmechanisms of absorption, distribution, metabolization and effects exerted inthe organism. Drosophila melanogaster has been widely used as a model to studythe pathophysiology induced by several substances, e.g. nicotine. This work aimsto provide information about the effects of this component of tobacco in theheart. We explored the genetic relevance of the two subunits (α1 and α7) of thenicotine receptors in the cardiac response of Drosophila melanogaster exposedto nicotine. We evaluated intracellular calcium handling, the phenomenonunderlying of heart performance, by means of a cardiac targeted genetically-encodedreporter system, TinC-Gal4-UAS-GCaMP3. Seven-days-old adult flies expressing asiRNA targeted to the α1/7 subunits of the nicotine receptor were compared towild-type individuals to evaluate the impact of subunits downregulation. Apulse of nicotine was spiked to the semi-intact preparation of the heart (1.69mM, final concentration) to exert acute effects on heart activity.The additionof nicotine incremented the heart rate (89.14±9.36vs 107.86±11.18 beats/min n=9-10) and accelerated themaximal velocities of contraction and relaxation (dΔF/dtmax: 0.164±0.02 vs 0.213±0.02; -dΔF/dtmax: -0.118±0.015 vs -0.181±0.015 n=9-10) and relaxation time in wild-type flies (0.187±0.025vs 0.12±0.004n=8). These effects were abolished when α1/7 subunits of the nicotinereceptor were downregulated. Paired Student´s t-test was used for statisticalanalysis, where p values<0.05 were considered statistically significant.These resultssuggest that nicotine´s effect on cardiac performance might be mediated by α1/7subunits of the nicotine receptor in the Drosophila Melanogaster´s heart. Weplanned further experiments to test if this can be reproduced in mammalianhearts, as for example in mice.