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

MANUELA SANTALLA; LUCÍA E. PAGOLA; IVANA M. GÓMEZ; DARÍO BALCAZAR; CARLOS A. VALVERDE; PAOLA FERRERO

Otro; Reunión Anual de Sociedades de Biociencias; 2020

Sociedad Argentina de Fisiología (SAFIS)- Sociedad Argentina de Inmunología (SAI)- Sociedad Argentina de Investigación Clínica (SAIC)

The relationship between substances consumed by humans and their impact on health has been explored in different animal models in an attempt to deepen on mechanisms of absorption, distribution, metabolization and effects exerted in the organism. Drosophila melanogaster has been widely used as a model to study the pathophysiology induced by several substances, e.g. nicotine. This work aims to provide information about the effects of this component of tobacco in the heart. We explored the genetic relevance of the two subunits (α1 and α7) of the nicotine receptors in the cardiac response of Drosophila melanogaster exposed to nicotine. We evaluated intracellular calcium handling, the phenomenon underlying of heart performance, by means of a cardiac targeted genetically-encoded reporter system, TinC-Gal4-UAS-GCaMP3. Seven-days-old adult flies expressing a siRNA targeted to the α1/7 subunits of the nicotine receptor were compared to wild-type individuals to evaluate the impact of subunits downregulation. A pulse of nicotine was spiked to the semi-intact preparation of the heart (1.69 mM, final concentration) to exert acute effects on heart activity. The addition of nicotine incremented the heart rate (89.14±9.36 vs 107.86±11.18 beats/min n=9-10) and accelerated the maximal 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±0.025 vs 0.12±0.004 n=8). These effects were abolished when α1/7 subunits of the nicotine receptor were downregulated. Paired Student´s t-test was used for statistical analysis, where p values