Study of ATP-sensitive potassium channel in constriction of ductus arteriosus

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461648
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Ishii Tetsuko 東京女子医科大学, 医学部, 講師 (00360157)
• Co-Investigator(Renkei-kenkyūsha): MOMMA Kazuo 東京女子医科大学, 医学部・循環器小児科, 名誉教授 (80075233)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 動脈管 / KATP channel

Outline of Final Research Achievements

ATP-sensitive potassium channels expressed in vascular smooth muscle cells are mainly composed of Kir6.1 and SUR2 subunits. Expression of Kir6.1 and SUR2 transcripts in ductus arteriosus (DA), main pulmonary artery (PA), and descending aorta (dAo) in rat immature and mature fetuses, and newborns were determined using real-time PCR. Both Kir6.1 and SUR2 transcripts are expressed in the DA higher than PA and dAo in the fetuses and newborns. Unidentified SUR2 transcript variants are expressed in the immature fetal DA, specifically.
Glibenclamide, an inhibitor of ATP-sensitive potassium channel, directly injected intraperitoneally to fetus rats, constricted DA in near-term and preterm. Effect of glibenclamide in the DA was dose-dependently. With clinical dose (1mg/kg), DA diameter was 70%, and with 100mg/kg, DA closed completely. Glibenclamide closes neonatal DA dose-dependently in hypoxia but not following prenatal chronic exposure to indomethacin.

Free Research Field

循環器小児科学