Impairment of IKCachannels contributes to uteroplacental endothelial dysfunction in rat diabetic pregnancy
| Autor: | Julie Phillips, Gabriela Goloman, Natalia I. Gokina, Kelsey Veilleux, Adrian D. Bonev, Karen H. Oppenheimer, Alexander P. Gokin |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Small-Conductance Calcium-Activated Potassium Channels Physiology Vascular Biology and Microcirculation Myocytes Smooth Muscle Action Potentials Diabetes Mellitus Experimental Preeclampsia Rats Sprague-Dawley Pregnancy Physiology (medical) Diabetes mellitus Internal medicine Potassium Channel Blockers Animals Medicine Placental Circulation Patch clamp Endothelial dysfunction Cells Cultured Membrane potential business.industry Endothelial Cells medicine.disease Rats Vasodilation Endocrinology Calcium Female Endothelium Vascular Cardiology and Cardiovascular Medicine business Complication Diabetic pregnancy |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 309:H592-H604 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00901.2014 |
| Popis: | Diabetes in rat pregnancy is associated with impaired vasodilation of the maternal uteroplacental vasculature. In the present study, we explored the role of endothelial cell (EC) Ca2+-activated K+channels of small conductance (SKCachannels) and intermediate conductance (IKCachannels) in diabetes-induced uterine vascular dysfunction. Diabetes was induced by injection of streptozotocin to second-day pregnant rats and confirmed by the development of maternal hyperglycemia. Control rats were injected with citrate buffer. Changes in smooth muscle cell intracellular Ca2+concentration, membrane potential, and vasodilation induced by SKCa/IKCachannel activators were studied in uteroplacental arteries of control and diabetic rats. The impact of diabetes on SKCa- and IKCa-mediated currents was explored in freshly dissociated ECs. NS309 evoked a potent vasodilation that was effectively inhibited by TRAM-34 but not by apamin. NS309-induced smooth muscle cell intracellular Ca2+concentration, membrane potential, and dilator responses were significantly diminished by diabetes; N-cyclohexyl- N-2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidinamine (CyPPA)-evoked responses were not affected. Ca2+-activated ion currents in ECs were insensitive to paxilline, markedly inhibited by charybdotoxin (ChTX), and diminished by apamin. NS309-induced EC currents were generated mostly due to activation of ChTX-sensitive channels. Maternal diabetes resulted in a significant reduction in ChTX-sensitive currents with no effect on apamin-sensitive or CyPPA-induced currents. We concluded that IKCachannels play a prevalent role over SKCachannels in the generation of endothelial K+currents and vasodilation of uteroplacental arteries. Impaired function of IKCachannels importantly contributes to diabetes-induced uterine endothelial dysfunction. Therapeutic restoration of IKCachannel function may be a novel strategy for improvement of maternal uteroplacental blood flow in pregnancies complicated by diabetes. |
| Databáze: | OpenAIRE |
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