Alterations of ATP-sensitive K+ channels in human umbilical arterial smooth muscle during gestational diabetes mellitus

Abstract

We investigated the alterations of ATP-sensitive K⁺ (K_ATP) channels in human umbilical arterial smooth muscle cells during gestational diabetes mellitus (GDM). The amplitude of the K_ATP current induced by application of the K_ATP channel opener pinacidil (10 μM) was reduced in the GDM group than in the control group. Pinacidil-induced vasorelaxation was also predominant in the normal group compared with the GDM group. Reverse transcription polymerase chain reaction and Western blot analysis suggested that the expression of K_ATP channel subunits such as Kir6.1, Kir6.2, and SUR2B were decreased in the GDM group relative to the normal group. The application of forskolin and adenosine, which activates protein kinase A (PKA) and thereby K_ATP channels, elicited K_ATP current in both the normal and GDM groups. However, the current amplitudes were not different between the normal and GDM groups. In addition, the expression levels of PKA subunits were not altered between the two groups. These results suggest that the reduction of K_ATP current and K_ATP channel-induced vasorelaxation are due to the decreased expression of K_ATP channels, not to the impairment of K_ATP-related signaling pathways.

Keywords: ATP-sensitive K+ channels; Gestational diabetes mellitus; Protein kinase A; Umbilical artery.