Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic, and hypertensive pregnancies

Vladimir Djokić; Miloć Gostimirović; Jovana Rajković; Jelena Rakočević; Milica Labudović-Borović; Svetlana Janković; Jelena Stanišić; Milan Kostić; Miloš Djurić; Ljiljana Gojković-Bukarica

doi:10.2298/VSP211014005D

Vladimir Djokić University of Belgrade, Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology
Miloć Gostimirović University of Belgrade, Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology
Jovana Rajković University of Belgrade, Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology
Jelena Rakočević University of Belgrade, Faculty of Medicine, Institute of Histology and Embryology “Aleksandar Dj. Kostić”
Milica Labudović-Borović University of Belgrade, Faculty of Medicine, Institute of Histology and Embryology “Aleksandar Dj. Kostić”
Svetlana Janković University of Belgrade, Faculty of Medicine, Department of Obstetrics and Gynecology “Narodni front”
Jelena Stanišić Vinča Institute of Nuclear Sciences, Belgrade, Serbia
Milan Kostić Vinča Institute of Nuclear Sciences, Belgrade, Serbia
Miloš Djurić University of Belgrade, Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology
Ljiljana Gojković-Bukarica University of Belgrade, Faculty of Medicine, Institute of Pharmacology, Clinical Pharmacology and Toxicology

DOI: https://doi.org/10.2298/VSP211014005D

Keywords: diabetes mellitus;, humans;, hypertension;, pregnancy;, umbilical veins

Abstract

Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type currents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collectively, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment.

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