Selective activation of the G-protein-coupled estrogen receptor (GPER) decreases cardiac contractility through inhibition of the L-type calcium channel (ICa) via Nitric Oxide Synthase

ALEJANDRO MARTÍN IBAÑEZ; MARÍA SOFÍA ESPEJO; ERNESTO ALEJANDRO AIELLO; LEANDRO DÍAZ ZEGARRA; VERÓNICA DE GIUSTI

Rosario

Congreso; SAFIS ANNUAL MEETING ROSARIO 2019; 2019

Sociedad Argentina de Fisiología

GPER was described as an orphan membrane receptor associated with protein G. Years later, estradiol was proposed as a possible ligand. It has been shown that the activation of GPER by its synthetic agonist G1 has cardioprotective effects. However, the mechanisms involved in these effects have not been fully clarified. Therefore, we propose the objective of evaluating the role of GPER activation on baseline cardiac contractility. For this, rat heart ventricular myocytes loaded with the fluorescent calcium indicator FURA-2 were used. Sarcomeric shortening (SS) and transient changes in intracellular calcium concentration (Ca2+i) were measured by video camera and epifluorescence, respectively. The influx of calcium through the L-type channel (ICa) was also evaluated by recording ionic currents with the patch-clamp technique. Stimulation of the GPER receptor with G1 (1 M) caused a significant decrease in baseline contractility (% of effect (n=15): -34.0±6.0, p0.05 respect to Ctrl). With the hypothesis that the L-type calcium channel was being affected by the GPER pathway, we decided to study the activity of this channel. G1 induced a significant decrease in ICa (pA/pF 0 mV, Ctrl: 4.44±0.71; G1: 3.44±0.47; n=14; p0.05). Finally, thinking that a possible pathway involves Nitric Oxide Synthase (NOS), the experiments were performed in the presence of the NOS inhibitor, L-NAME (10 M). No differences were found in baseline contractility respect to L-NAME + G1 (% of effect (n=9): L-NAME+G1: 4.73±2.56, p>0.05 respect to Ctrl), in Ca2+i (% of effect (n=10): L-NAME+G1: -0.11±2.60, p>0.05 respect to Ctrl) and ICa (pA/pF 0 mV, L-NAME: 2.92±0.25, L-NAME+G1: 2.71±0.25, n=12, p>0.05). We conclude that the selective activation of cardiac GPER induces a decrease in contractility as a consequence of the inhibition of ICa, through activated NOS, however other intermediaries are not ruled out.