Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

34-POS Board 34 Role of Calcium-activated Potassium Channels in L-arginine/NO Pathway Regulation by Insulin in Human Fetal Endothelium. Emerita Basualto 1 , Susana Rojas 1 , Marcela Cid 3 , Marcelo Gonzalez 1,2 . 1 University of Concepcion, Concepción, Chile, 2 Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillan, Chile, 3 University of Concepcion, Concepcion, Chile. The regulation of vascular tone of placenta is a key mechanism for an adequate nutrition of the fetus and this mechanism is regulated by paracrine and endocrine signals. Between these signals, insulin is an hormone that have a important role, especially when the fetus develops his pancreas, acting directly on endothelial cells of umbilical cord and placenta. A main mechanism for regulation of vascular tone is related with the endothelial activity of calcium-activated potassium channels (KCa). In this study we want to determine if the mechanism of relaxation induced by insulin is dependent of KCa channels. Placenta and umbilical cords were obtained from normal pregnancies for placental vascular reactivity assays and isolation of human umbilical vein endothelial cells (HUVEC). Isometric tension and placental pressure were determined through wire myogaphy and isolated cotyledon perfusion, respectively, in vessels incubated with insulin and/or tetra ethyl ammonium (TEA, K + channels inhibitor), iberiotoxin (BKCa ihibitor) and Tram-34 (SKCa inhibitor). In HUVEC, after similar treatment, the plasma membrane polarity changes (with DiBAC4(3) dye), nitric oxide synthesis (with DAF) and L-arginine transport were determined. Insulin induces relaxation in placental vein and lower perfusion pressure in placenta, both effects were blocked with KCa channels inhibitors. In HUVEC, the stimulation of insulin on NO synthesis and L-arginine transport were decreased with iberiotoxin and Tram-34. In plasma membrane polarity, the co-incubation with insulin prevent the depolarization induced by Tram-34 and iberiotoxin. The vasodilatation induced by insulin is a mechanism that depends on L-arginine transport and NO synthesis. Our results showed that this mechanism could require a previous step of plasma membrane hyperpolarization induced by activation of BKCa or SKCa in human fetal endothelium. Supported by VRID-Enlace 216.033.108-1.0 and VRID-Asociativo 213.A84.014-1.0, Universidad de Concepción, Chile.

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