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Experimental Diabetes Impairs Endothelial IKCa Channel Function in Uteroplacental Arteries from Pregnant Rats
Author(s) -
Gokitalia I.,
Phillips Julie K.,
Bonev Adrian D.,
Gokin Alexander P.,
Goloman Gabriela
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.687.8
Subject(s) - medicine , endocrinology , diabetes mellitus , vasodilation , apamin , charybdotoxin , potassium channel , endothelial dysfunction , streptozotocin
Diabetic pregnancy is associated with adverse fetal complications in part due to impaired uteroplacental blood flow. In this study, we explored the role of endothelial cell (EC) SK Ca and IK Ca channels in impaired uteroplacental vasodilation during diabetic pregnancy. Diabetes was induced by i.p. injection of streptozotocin on 2 nd day of pregnancy. We tested the effects of NS309 and CyPPA on arterial diameters, SMC [Ca 2+ ] i and membrane potential using fura 2‐based fluorescence and glass microelectrodes. Whole‐cell patch clamp methodology was used to characterize SK Ca and IK Ca channel function in isolated ECs of control and diabetic rats. NS309‐induced vasodilation, SMC [Ca 2+ ] i reduction and hyperpolarization were significantly impaired by diabetic pregnancy. Maximal responses to CyPPA were 50–60% smaller than those to NS309, and were not affected by diabetes. NS309 markedly potentiated endothelial K + currents in ECs from control and diabetic rats. K + currents were inhibited by appr. 80% and 20% with charybdotoxin (CTX) and apamin, respectively. Only CTX‐sensitive currents were reduced in diabetic ECs (6.5 ± 1.6 vs. 11.1 ± 1.1 pA/pF at 0 mV; n = 7). In summary, IK Ca channels play a predominant role in the control of uteroplacental dilatation. Impaired function of IK Ca channels contributes to diabetes‐induced endothelial dysfunction in the maternal uteroplacental circulation. Supported by NIH HL088245