Downregulation of large-conductance Ca2+-activated K+ channels in human umbilical arterial smooth muscle cells in gestational diabetes mellitus.

Abstract

AIMS:

We investigated the changes in large-conductance Ca2+-activated K+ (BKCa) channels from human umbilical arterial smooth muscle cells experiencing gestational diabetes mellitus (GDM).

MAIN METHODS:

Whole-cell patch-clamp technique, arterial tone measurement, RT-PCR, Quantitative real-time PCR, western blot were performed in human umbilical arterial smooth muscle cells.

KEY FINDINGS:

Whole-cell BKCa current density was decreased in the GDM group compared with the normal group. The vasorelaxant effects of the synthetic BKCa channel activator NS-1619 (10 μM) were impaired in the GDM group compared with the normal group. Reverse-transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and western blot analyses suggested that the mRNA, total RNA, and protein expression levels of the BKCa channel were decreased in the GDM group relative to the normal group. In addition, the expression levels of protein kinase A and protein kinase G, which regulate BKCa channel activity, remained unchanged between the groups. Applying the BKCa channel inhibitor paxilline (10 μM) induced vasoconstriction and membrane depolarization of isolated umbilical arteries in the normal group but showed less of an effect on umbilical arteries in the GDM group.

SIGNIFICANCE:

Our results demonstrate for the first time impaired BKCa current and BKCa channel-induced vasorelaxation activities that were not caused by impaired BKCa channel-regulated protein kinases, but by decreased expression of the BKCa channels, in the umbilical arteries of GDM patients.

• Authors: Hongliang Li, Jin Ryeol An, Mi Seon Seo, Minji Kang, Ryeon Heo, Seojin Park, Seo-Yeong Mun, Young Min Bae, Eun-Taek Han, Jin-Hee Han, Wanjoo Chun, Sung Hun Na, Won Sun Park
• Journal: Life sciences (Life Sci) Vol. 288 Pg. 120169 (Jan 01 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34822796 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Indoles
• Large-Conductance Calcium-Activated Potassium Channels
• Potassium Channel Blockers
• paxilline
• Cyclic AMP-Dependent Protein Kinases
• Cyclic GMP-Dependent Protein Kinases

Topics

• Adult
• Case-Control Studies
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Cyclic GMP-Dependent Protein Kinases (metabolism)
• Diabetes, Gestational (drug therapy, metabolism, pathology)
• Female
• Gene Expression Regulation (drug effects)
• Humans
• Indoles (pharmacology)
• Large-Conductance Calcium-Activated Potassium Channels (antagonists & inhibitors, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism, pathology)
• Potassium Channel Blockers (pharmacology)
• Pregnancy
• Umbilical Arteries (drug effects, metabolism, pathology)
• Vasoconstriction