Pregnancy-induced hypertension decreases K1.3 potassium channel expression and function in human umbilical vein smooth muscle.

Voltage-gated potassium (K) channels are the largest superfamily of potassium (K) channels. A variety of K 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 K1-4 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 K 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 K1.2 and K1.3 channels, significantly antagonized pinacidil-induced vasorelaxation in normal pregnancy, while in HUVs from GDM and PIH that was not the case, indicating damage of K1.2 and K1.3 channel function. Immunohistochemistry and Western blot revealed similar expression of K1.2 channels in all groups. The expression of K1.3 subunit was significantly decreased in PIH, while it remained unchanged in GDM compared to normal pregnancy. Phrixotoxin, specific blocker of K4.2 and K4.3 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 K1.3 channels in HUV during PIH may be important pathophysiological mechanism contributing to an increased risk of adverse pregnancy outcomes.