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• W2079247844 abstract "There is a well-characterized membrane chloride current (ICl,cAMP) in the heart that can be activated by β-adrenergic agonists and is due to expression of the cardiac isoform of the epithelial cystic fibrosis transmembrane conductance regulator (CFTR). We have investigated whether 17β-estradiol (E2) modulates ICl,cAMP in single ventricular myocytes. Under whole-cell tight-seal voltage-clamp conditions, ICl,cAMP was evoked by exposing cells to 20 nM isoprenaline. On the addition of 30 μM E2, membrane slope conductance, measured at potentials near 0 mV, increased over that induced by isoprenaline alone by 2.46 ± 0.16 (p < 0.001). The effects of E2 were concentration-dependent and described by a Hill Plot with an EC50 of 8.2 μM and a Hill coefficient of 1.63. The application of membrane-impermeant E2 conjugated to bovine serum albumin (E2-BSA) potentiated isoprenaline-evoked ICl,cAMP by approximately the same degree as that for the equivalent level of free E2. Cell surface binding was observed with confocal microscopy by using BSA-FITC tagged E2. This binding was inhibited by nonlabeled, nonconjugate E2, the specific E2 antagonist ICI 182,780, and incubation of E2coBSA with a specific anti-E2 antibody (E2885). ICI 182,780 (100 μM) significantly reduced the increase in ICl,cAMP evoked by 10 μM E2 to 1.46 ± 0.10 (p < 0.02). The preincubation of myocytes with the NOS inhibitor N-ω-nitro-arginine (L-NNA, 1 mM) reduced the potentiation of ICl,cAMP by 30 μM E2, to 1.93 ± 0.06 (p < 0.02), and for 10 μM E2, to 1.32 ± 0.05 (p < 0.002). E2 also increased ICl,cAMP evoked by bath application of 0.5 μM Forskolin. These experiments demonstrate that, under our experimental conditions, E2 dramatically increases ICl,cAMP in ventricular myocytes by mechanisms involving a contribution by NOS, but that can be only partially accounted for through binding to classical plasma membrane estrogen receptor sites. This potentiation of ICl,cAMP by E2 may play a significant role in the observed clinical actions of E2 on the incidence of cardiac arrhythmias and hypertrophy." @default.
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• W2079247844 date "2006-01-01" @default.
• W2079247844 modified "2023-10-17" @default.
• W2079247844 title "17β-Estradiol Potentiates the Cardiac Cystic Fibrosis Transmembrane Conductance Regulator Chloride Current in Guinea-pig Ventricular Myocytes" @default.
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• W2079247844 doi "https://doi.org/10.2170/physiolsci.r2131" @default.
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