Pflügers Archiv - European Journal of Physiology

, Volume 470, Issue 9, pp 1325–1333 | Cite as

Alterations of ATP-sensitive K+ channels in human umbilical arterial smooth muscle during gestational diabetes mellitus

  • Hongliang Li
  • Sung Eun Shin
  • Mi Seon Seo
  • Jin Ryeol An
  • Kwon-Soo Ha
  • Eun-Taek Han
  • Seok-Ho Hong
  • Jeeyoung Kim
  • Mi-Jin Yim
  • Jeong Min Lee
  • Tae Gyu An
  • Jihan Jeon
  • Se Jin Lee
  • Sung Hun NaEmail author
  • Won Sun ParkEmail author
Ion channels, receptors and transporters
Part of the following topical collections:
  1. Topical Collection: Ion channels, receptors and transporters


We investigated the alterations of ATP-sensitive K+ (KATP) channels in human umbilical arterial smooth muscle cells during gestational diabetes mellitus (GDM). The amplitude of the KATP current induced by application of the KATP channel opener pinacidil (10 μM) was reduced in the GDM group than in the control group. Pinacidil-induced vasorelaxation was also predominant in the normal group compared with the GDM group. Reverse transcription polymerase chain reaction and Western blot analysis suggested that the expression of KATP channel subunits such as Kir6.1, Kir6.2, and SUR2B were decreased in the GDM group relative to the normal group. The application of forskolin and adenosine, which activates protein kinase A (PKA) and thereby KATP channels, elicited KATP current in both the normal and GDM groups. However, the current amplitudes were not different between the normal and GDM groups. In addition, the expression levels of PKA subunits were not altered between the two groups. These results suggest that the reduction of KATP current and KATP channel-induced vasorelaxation are due to the decreased expression of KATP channels, not to the impairment of KATP-related signaling pathways.


ATP-sensitive K+ channels Umbilical artery Gestational diabetes mellitus Protein kinase A 


Sources of funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Education: 2016-R1D1A3B03930169, 2017-R1D1A1B03028467) (Ministry of Science, ICT and Future Planning: 2015-R1A4A1038666).

Compliance with ethical standards

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Supplementary material

424_2018_2154_MOESM1_ESM.pptx (661 kb)
Figure S1 (PPTX 661 kb)


  1. 1.
    Akrouh A, Halcomb SE, Nichols CG, Sala-Rabanal M (2009) Molecular biology of K(ATP) channels and implications for health and disease. IUBMB Life 61:971–978CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Aziz Q, Thomas AM, Gomes J, Ang R, Sones WR, Li Y, Ng KE, Gee L, Tinker A (2014) The ATP-sensitive potassium channel subunit, Kir6.1, in vascular smooth muscle plays a major role in blood pressure control. Hypertension 64:523–529CrossRefPubMedGoogle Scholar
  3. 3.
    Babenko AP, Aguilar-Bryan L, Bryan J (1998) A view of sur/KIR6.X, KATP channels. Annu Rev Physiol 60:667–687CrossRefPubMedGoogle Scholar
  4. 4.
    Binbir B, Yeniel AO, Ergenoglu AM, Kazandi M, Akercan F, Sagol S (2012) The role of umbilical cord thickness and HbA1c levels for the prediction of fetal microsomal in patients with gestational diabetes mellitus. Arch Gynecol Obstet 285:635–639CrossRefPubMedGoogle Scholar
  5. 5.
    Garg V, Jiao J, Hu K (2009) Regulation of ATP-sensitive K+ channels by caveolin-enriched microdomains in cardiac myocytes. Cardiovasc Res 82:51–58CrossRefPubMedGoogle Scholar
  6. 6.
    Ghosh M, Hanna ST, Wang R, McNeill JR (2004) Altered vascular reactivity and KATP channel currents in vascular smooth muscle cells from deoxy-corticosterone acetate (DOCA)-salt hypertensive rats. J Cardiovasc Pharmacol 44:525–531CrossRefPubMedGoogle Scholar
  7. 7.
    Hayabuchi Y, Davies NW, Standen NB (2001) Angiotensin II inhibits rat arterial KATP channels by inhibiting steady-state protein kinase A activity and activating protein kinase Ce. J Physiol 530:193–205CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y (2010) Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiol Rev 90:291–366CrossRefPubMedGoogle Scholar
  9. 9.
    Kleppisch T, Nelson MT (1995) Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase. Proc Natl Acad Sci U S A 92:12441–12445CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ko EA, Han J, Jung ID, Park WS (2008) Physiological roles of K+ channels in vascular smooth muscle cells. J Smooth Muscle Res 44:65–81CrossRefPubMedGoogle Scholar
  11. 11.
    Li J, Chen YP, Dong YP, Yu CH, Lu YP, Xiao XM, Hocher B (2014) The impact of umbilical blood flow regulation on fetal development differs in diabetic and non-diabetic pregnancy. Kidney Blood Press Res 39:369–377CrossRefPubMedGoogle Scholar
  12. 12.
    Li S, Chen S, Yang W, Liao L, Li S, Li J, Zheng Y, Zhu D (2017) Allicin relaxes isolated mesenteric arteries through activation of PKA-KATP channel in rat. J Recept Signal Transduct Res 37:17–24CrossRefPubMedGoogle Scholar
  13. 13.
    Liu SF, Tian HM, Liao DQ, Chen YF, Gou ZP, Xie XY, Li XJ (2015) The effect of gliquidone on KATP channels in pancreatic β-cells, cardiomyocytes, and vascular smooth muscle cells. Diabetes Res Clin Pract 109:334–339CrossRefPubMedGoogle Scholar
  14. 14.
    Liu F, Liu Y, Lai YP, Gu XN, Liu DM, Yang M (2016) Fetal hemodynamics and fetal growth indices by ultrasound in late pregnancy and birth weight in gestational diabetes mellitus. Chin Med J 129:2109–2114CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Macaulay S, Dunger DB, Norris SA (2014) Gestational diabetes mellitus in Africa: a systematic review. PLoS One 9:e97871CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Malo MS (2015) A high level of intestinal alkaline phosphatase is protective against type 2 diabetes mellitus irrespective of obesity. EBioMedicine 2:2016–2023CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Martín P, Rebolledo A, Palomo AR, Moncada M, Piccinini L, Milesi V (2014) Diversity of potassium channels in human umbilical artery smooth muscle cells: a review of their roles in human umbilical artery contraction. Reprod Sci 21:432–441CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Namavar Jahromi B, Ahmadi N, Cohan N, Jahromi MR (2011) Comparison of the umbilical artery blood gas, nucleated red blood cell, C-reactive protein, and white blood cell differential counts between neonates of diabetic and nondiabetic mothers. Taiwan J Obstet Gynecol 50:301–305CrossRefPubMedGoogle Scholar
  19. 19.
    Nichols CG, Singh GK, Grange DK (2013) KATP channels and cardiovascular disease: suddenly a syndrome. Circ Res 112:1059–1072CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Park WS, Hong DH, Son YK, Kim MH, Jeong SH, Kim HK, Kim N, Han J (2012) Alteration of ATP-sensitive K+ channels in rabbit aortic smooth muscle during left ventricular hypertrophy. Am J Phys 303:C170–C178CrossRefGoogle Scholar
  21. 21.
    Pietryga M, Brazert J, Wender-Ozegowska E, Dubiel M, Gudmundsson S (2006) Placenta Doppler velocimetry in gestational diabetes mellitus. J Perinat Med 34:108–110CrossRefPubMedGoogle Scholar
  22. 22.
    Quayle JM, Bonev AD, Brayden JE, Nelson MT (1994) Calcitonin-gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth-muscle via protein-kinase-A. J Physiol Lond 475:9–13CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Quayle JM, Nelson MT, Standen NB (1997) ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. Physiol Rev 77:1165–1232CrossRefPubMedGoogle Scholar
  24. 24.
    Shand AW, Bell JC, McElduff A, Morris J, Roberts CL (2008) Outcomes of pregnancies in women with pre-gestational diabetes mellitus and gestational diabetes mellitus: a population-based study in New South Wales, Australia, 1998-2002. Diabet Med 25:708–715CrossRefPubMedGoogle Scholar
  25. 25.
    Shi Y, Wu Z, Cui N, Shi W, Yang Y, Zhang X, Rojas A, Ha BT, Jiang C (2007) PKA phosphorylation of SUR2B subunit underscores vascular KATP channel activation by beta-adrenergic receptors. Am J Physiol Regul Integr Comp Physiol 293:1205–1214CrossRefGoogle Scholar
  26. 26.
    Shin HD, Park BL, Shin HJ, Kim JY, Park S, Kim B, Kim SH (2010) Association of KCNQ1 polymorphisms with the gestational diabetes mellitus in Korean women. J Clin Endocrinol Metab 95:445–449CrossRefPubMedGoogle Scholar
  27. 27.
    Spivack M (1946) The anatomic peculiarities of the human umbilical cord and their clinical significance. Am J Obstet Gynecol 52:387–401CrossRefPubMedGoogle Scholar
  28. 28.
    Stanley JL, Cheung CC, Rueda-Clausen CF, Sankaralingam S, Baker PN, Davidge ST (2011) Effect of gestational diabetes on maternal artery function. Reprod Sci 18:342–352CrossRefPubMedGoogle Scholar
  29. 29.
    Voskamp BJ, Fleurke-Rozema H, Oude-Rengerink K, Snijders RJ, Bilardo CM, Mol BW, Pajkrt E (2013) Relationship of isolated single umbilical artery to fetal growth, aneuploidy and perinatal mortality: systematic review and meta-analysis. Ultrasound Obstet Gynecol 42:622–628CrossRefPubMedGoogle Scholar
  30. 30.
    Ye D, Zhou W, Lee HC (2005) Activation of rat mesenteric arterial KATP channels by 11, 12-epoxyeicosatrienoic acid. Am J Physiol Heart Circ Physiol 288:358–364CrossRefGoogle Scholar
  31. 31.
    Zhou Q, Zhang K, Li W, Liu JT, Hong J, Qin SW, Ping F, Sun ML, Nie M (2009) Association of KCNQ1 gene polymorphism with gestational diabetes mellitus in a Chinese population. Diabetologia 52:2466–2468CrossRefPubMedGoogle Scholar
  32. 32.
    Zimmermann PA, Knot HJ, Stevenson AS, Nelson MT (1997) Increased myogenic tone and diminished responsiveness to ATP-sensitive K+ channel openers in cerebral arteries from diabetic rats. Circ Res 81:996–1004CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hongliang Li
    • 1
  • Sung Eun Shin
    • 1
  • Mi Seon Seo
    • 1
  • Jin Ryeol An
    • 1
  • Kwon-Soo Ha
    • 2
  • Eun-Taek Han
    • 3
  • Seok-Ho Hong
    • 4
  • Jeeyoung Kim
    • 4
  • Mi-Jin Yim
    • 5
  • Jeong Min Lee
    • 5
  • Tae Gyu An
    • 6
  • Jihan Jeon
    • 6
  • Se Jin Lee
    • 6
  • Sung Hun Na
    • 6
    Email author
  • Won Sun Park
    • 1
    Email author
  1. 1.Department of PhysiologyKangwon National University School of MedicineChuncheonSouth Korea
  2. 2.Department of Molecular and Cellular BiochemistryKangwon National University School of MedicineChuncheonSouth Korea
  3. 3.Department of Medical Environmental Biology and Tropical MedicineKangwon National University School of MedicineChuncheonSouth Korea
  4. 4.Department of Internal MedicineKangwon National University School of MedicineChuncheonSouth Korea
  5. 5.Department of Applied ResearchNational Marine Biodiversity Institute of KoreaSeocheonSouth Korea
  6. 6.Department of Obstetrics and Gynecology, Kangwon National University HospitalKangwon National University School of MedicineChuncheonSouth Korea

Personalised recommendations