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Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle.

Abstract：

:Voltage-gated potassium (Kv) channels are the largest superfamily of potassium (K) channels. A variety of Kv channels are expressed in the vascular smooth muscle cells (SMC). Studies have shown that gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) cause various changes in the human umbilical vein (HUV). Recently, we have shown that 4-AP, a nonspecific Kv1-4 channel inhibitor, significantly decreases vasorelaxation induced by K channel opener pinacidil in vascular SMCs of the HUVs from normal pregnancies, but not in GDM and PIH. The goal of this study was to provide more detailed insight in the Kv channel subtypes involved in pinacidil-induced vasodilation of HUVs, as well as to investigate potential alterations of their function and expression during GDM and PIH. Margatoxin, a specific blocker of Kv1.2 and Kv1.3 channels, significantly antagonized pinacidil-induced vasorelaxation in normal pregnancy, while in HUVs from GDM and PIH that was not the case, indicating damage of Kv1.2 and Kv1.3 channel function. Immunohistochemistry and Western blot revealed similar expression of Kv1.2 channels in all groups. The expression of Kv1.3 subunit was significantly decreased in PIH, while it remained unchanged in GDM compared to normal pregnancy. Phrixotoxin, specific blocker of Kv4.2 and Kv4.3 channels, did not antagonize response to pinacidil in any of the groups. The major novel findings show that margatoxin antagonized pinacidil-induced relaxation in normal pregnancy, but not in GDM and PIH. Decreased expression of Kv1.3 channels in HUV during PIH may be important pathophysiological mechanism contributing to an increased risk of adverse pregnancy outcomes.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Djokic V,Jankovic S,Labudovic-Borovic M,Rakocevic J,Stanisic J,Rajkovic J,Novakovic R,Kostic M,Djuric M,Gostimirovic M,Gojkovic-Bukarica L

doi

10.1016/j.ejphar.2020.173281

subject

Has Abstract

pub_date

2020-09-05 00:00:00

pages

173281

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(20)30373-3

journal_volume

882

pub_type

杂志文章

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Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle.