Impaired KATP channel function in the fetoplacental circulation of patients with type 1 diabetes mellitus.
OBJECTIVE
The increased perinatal morbidity in diabetes may be partly related to vascular dysfunction. Because potassium channels play an important role in the regulation of vascular tone, this study explores the impact of diabetes on potassium channel function in the fetoplacental vascular bed.


METHODS
Vascular potassium channel function was investigated by ex vivo dual perfusion of isolated placental cotyledons (n = 47). Appropriate control experiments were carried out to exclude nonspecific effects.


RESULTS
Glibenclamide (KATP channel blocker) increased perfusion pressure to a maximum fetoplacental arterial pressure of 37 +/- 6 mm Hg in controls versus 15 +/- 6 mm Hg in diabetes (P < .05). 4-Aminopyridine (KV channel blocker) equally increased fetoplacental arterial pressure in controls, and in diabetes (21 +/- 4 mm Hg vs 22 +/- 2 mm Hg). Apamin and charybdotoxin (KCa channel blockers) caused a negligible rise in fetoplacental arterial pressure.


CONCLUSIONS
In the fetoplacental circulation, KATP channels and KV channels significantly contribute to baseline vascular tone. In diabetes, vascular KATP channel function is impaired.
Bisseling
Tanya M
TM
Department of Pharmacology-Toxicology, University Medical Center, Nijmegen, The Netherlands.
Versteegen
Marieke G
MG
van der Wal
Selina
S
Copius Peereboom-Stegeman
Jenny J H
JJ
Borggreven
Joop M P M
JM
Steegers
Eric A P
EA
van der Laak
Jeroen A W M
JA
Russel
Frans G M
FG
Smits
Paul
P
D015761:4-Aminopyridine / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D021041:Placental Circulation / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*
D015221:Potassium Channels; D018999:Charybdotoxin; D015761:4-Aminopyridine; D005905:Glyburide