Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle
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2020
Authors
Đokić, VladimirJanković, Svetlana
Labudović-Borović, Milica
Rakočević, Jelena T.
Stanišić, Jelena
Rajković, Jovana
Novaković, Radmila
Kostić, Milan
Đurić, Miloš
Gostimirović, Miloš
Gojković-Bukarica, Ljiljana
Article (Published version)
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© 2020 Elsevier B.V.
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Voltage-gated potassium (K ) channels are the largest superfamily of potassium (K) channels. A variety of K channels are expressed in the vascular smooth muscle cells (SMC). Studies have shown that gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) cause various changes in the human umbilical vein (HUV). Recently, we have shown that 4-AP, a nonspecific K 1-4 channel inhibitor, significantly decreases vasorelaxation induced by K channel opener pinacidil in vascular SMCs of the HUVs from normal pregnancies, but not in GDM and PIH. The goal of this study was to provide more detailed insight in the K channel subtypes involved in pinacidil-induced vasodilation of HUVs, as well as to investigate potential alterations of their function and expression during GDM and PIH. Margatoxin, a specific blocker of K 1.2 and K 1.3 channels, significantly antagonized pinacidil-induced vasorelaxation in normal pregnancy, while in HUVs from GDM and PIH that was not the case, indica...ting damage of K 1.2 and K 1.3 channel function. Immunohistochemistry and Western blot revealed similar expression of K 1.2 channels in all groups. The expression of K 1.3 subunit was significantly decreased in PIH, while it remained unchanged in GDM compared to normal pregnancy. Phrixotoxin, specific blocker of K 4.2 and K 4.3 channels, did not antagonize response to pinacidil in any of the groups. The major novel findings show that margatoxin antagonized pinacidil-induced relaxation in normal pregnancy, but not in GDM and PIH. Decreased expression of K 1.3 channels in HUV during PIH may be important pathophysiological mechanism contributing to an increased risk of adverse pregnancy outcomes.
Keywords:
Human umbilical vein / Gestational diabetes mellitus (GDM) / Pregnancy-induced hypertension (PIH) / K-v channel / Pinacidil / MargatoxinSource:
European Journal of Pharmacology, 2020, 882, 173281-Funding / projects:
- Development of new technology for production of red wine and diatery supplements reach with polyphenols with cardioprotective effects (RS-MESTD-Technological Development (TD or TR)-31020)
- Role of steroid hormones in neuroendocrine adaptation to stress and pathophysiology of metabolic syndrome - molecular mechanisms and clinical implications (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41009)
DOI: 10.1016/j.ejphar.2020.173281
ISSN: 0014-2999
PubMed: 32562800
WoS: 000554893000014
Scopus: 2-s2.0-85087840963
Institution/Community
VinčaTY - JOUR AU - Đokić, Vladimir AU - Janković, Svetlana AU - Labudović-Borović, Milica AU - Rakočević, Jelena T. AU - Stanišić, Jelena AU - Rajković, Jovana AU - Novaković, Radmila AU - Kostić, Milan AU - Đurić, Miloš AU - Gostimirović, Miloš AU - Gojković-Bukarica, Ljiljana PY - 2020 UR - https://vinar.vin.bg.ac.rs/handle/123456789/9048 AB - Voltage-gated potassium (K ) channels are the largest superfamily of potassium (K) channels. A variety of K channels are expressed in the vascular smooth muscle cells (SMC). Studies have shown that gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) cause various changes in the human umbilical vein (HUV). Recently, we have shown that 4-AP, a nonspecific K 1-4 channel inhibitor, significantly decreases vasorelaxation induced by K channel opener pinacidil in vascular SMCs of the HUVs from normal pregnancies, but not in GDM and PIH. The goal of this study was to provide more detailed insight in the K channel subtypes involved in pinacidil-induced vasodilation of HUVs, as well as to investigate potential alterations of their function and expression during GDM and PIH. Margatoxin, a specific blocker of K 1.2 and K 1.3 channels, significantly antagonized pinacidil-induced vasorelaxation in normal pregnancy, while in HUVs from GDM and PIH that was not the case, indicating damage of K 1.2 and K 1.3 channel function. Immunohistochemistry and Western blot revealed similar expression of K 1.2 channels in all groups. The expression of K 1.3 subunit was significantly decreased in PIH, while it remained unchanged in GDM compared to normal pregnancy. Phrixotoxin, specific blocker of K 4.2 and K 4.3 channels, did not antagonize response to pinacidil in any of the groups. The major novel findings show that margatoxin antagonized pinacidil-induced relaxation in normal pregnancy, but not in GDM and PIH. Decreased expression of K 1.3 channels in HUV during PIH may be important pathophysiological mechanism contributing to an increased risk of adverse pregnancy outcomes. T2 - European Journal of Pharmacology T1 - Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle VL - 882 SP - 173281 DO - 10.1016/j.ejphar.2020.173281 ER -
@article{ author = "Đokić, Vladimir and Janković, Svetlana and Labudović-Borović, Milica and Rakočević, Jelena T. and Stanišić, Jelena and Rajković, Jovana and Novaković, Radmila and Kostić, Milan and Đurić, Miloš and Gostimirović, Miloš and Gojković-Bukarica, Ljiljana", year = "2020", abstract = "Voltage-gated potassium (K ) channels are the largest superfamily of potassium (K) channels. A variety of K channels are expressed in the vascular smooth muscle cells (SMC). Studies have shown that gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) cause various changes in the human umbilical vein (HUV). Recently, we have shown that 4-AP, a nonspecific K 1-4 channel inhibitor, significantly decreases vasorelaxation induced by K channel opener pinacidil in vascular SMCs of the HUVs from normal pregnancies, but not in GDM and PIH. The goal of this study was to provide more detailed insight in the K channel subtypes involved in pinacidil-induced vasodilation of HUVs, as well as to investigate potential alterations of their function and expression during GDM and PIH. Margatoxin, a specific blocker of K 1.2 and K 1.3 channels, significantly antagonized pinacidil-induced vasorelaxation in normal pregnancy, while in HUVs from GDM and PIH that was not the case, indicating damage of K 1.2 and K 1.3 channel function. Immunohistochemistry and Western blot revealed similar expression of K 1.2 channels in all groups. The expression of K 1.3 subunit was significantly decreased in PIH, while it remained unchanged in GDM compared to normal pregnancy. Phrixotoxin, specific blocker of K 4.2 and K 4.3 channels, did not antagonize response to pinacidil in any of the groups. The major novel findings show that margatoxin antagonized pinacidil-induced relaxation in normal pregnancy, but not in GDM and PIH. Decreased expression of K 1.3 channels in HUV during PIH may be important pathophysiological mechanism contributing to an increased risk of adverse pregnancy outcomes.", journal = "European Journal of Pharmacology", title = "Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle", volume = "882", pages = "173281", doi = "10.1016/j.ejphar.2020.173281" }
Đokić, V., Janković, S., Labudović-Borović, M., Rakočević, J. T., Stanišić, J., Rajković, J., Novaković, R., Kostić, M., Đurić, M., Gostimirović, M.,& Gojković-Bukarica, L.. (2020). Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle. in European Journal of Pharmacology, 882, 173281. https://doi.org/10.1016/j.ejphar.2020.173281
Đokić V, Janković S, Labudović-Borović M, Rakočević JT, Stanišić J, Rajković J, Novaković R, Kostić M, Đurić M, Gostimirović M, Gojković-Bukarica L. Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle. in European Journal of Pharmacology. 2020;882:173281. doi:10.1016/j.ejphar.2020.173281 .
Đokić, Vladimir, Janković, Svetlana, Labudović-Borović, Milica, Rakočević, Jelena T., Stanišić, Jelena, Rajković, Jovana, Novaković, Radmila, Kostić, Milan, Đurić, Miloš, Gostimirović, Miloš, Gojković-Bukarica, Ljiljana, "Pregnancy-induced hypertension decreases Kv1.3 potassium channel expression and function in human umbilical vein smooth muscle" in European Journal of Pharmacology, 882 (2020):173281, https://doi.org/10.1016/j.ejphar.2020.173281 . .