TY  - JOUR
AU  - Đokić, Vladimir
AU  - Gostimirović, Miloš
AU  - Rajković, Jovana
AU  - Rakočević, Jelena
AU  - Labudović-Borović, Milica
AU  - Janković, Svetlana
AU  - Stanišić, Jelena
AU  - Kostić, Milan
AU  - Đurić, Miloš
AU  - Gojković-Bukarica, Ljiljana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11226
AB  - Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type cur-rents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collective-ly, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment.
AB  - Uvod/Cilj. Značajan niz dokaza ukazuje na to da su kanali Kv4.2 i Kv4.3 glavne komponente brzih prolazno- ispravljačkih struja kalijuma (struje tipa A). Pretpostavlja se da bi te struje mogle da budu uključene u održavanje membranskog potencijala ćelije, kao i u regulaciju propagacije i učestalosti akcionih potencijala. Međutim, vrlo malo se zna o prisustvu i funkciji struje tipa A u glatkim mišićima krvnih sudova čoveka, kao što je humana umbilikalna vena (HUV). S obzirom na njenu ključnu ulogu u adekvatnoj oksigenaciji fetusa, cilj rada bio je da se utvrdi da li su podtipovi kalijumovih kanala Kv4.2 i Kv4.3 prisutni u glatkim mišićima HUV-a i da se istraže potencijalne promene njihove ekspresije tokom patoloških stanja majke – gestacijskog dijabetesa melitusa (GDM) i arterijske hipertenzije (AH) izazvane trudnoćom (AHT). Metode. U istraživanje su uključene HUV sakupljene posle trudnoće zdravih porodilja, onih čije trudnoće su bile komplikovane GDM i AH. Svaka grupa sastojala se od 6 uzoraka HUV-a dobijenih iz 6 zdravih trudnoća, 6 trudnoća komplikovanih GDM i 6 trudnoća komplikovanih AH. Nakon farmakoloških analiza, urađene su imunohistohemijska (IH) analiza i Western blot. Rezultati. Primenom IH analize pokazan je sličan obrazac ekspresije obe podjedinice Kv4.2 i Kv4.3 kanala u glatkim mišićima HUV-a u svim grupama trudnica. Rezultati dobijeni Western blot-om bili su u skladu sa IH bojenjem. Ekspresija podjedinica Kv4.2 i Kv4.3 nije se značajno razlikovala između grupa trudnica. Zaključak. Ovo je prema našim saznanjima prva studija kojom je pokazano prisustvo Kv4.2 i Kv4.3 kalijumovih kanala u glatkim mišićima HUV-a zdravih porodilja, kao i onih porodilja čija je trudnoća bila praćena prisustvom GDM ili AHT. Ti kanali su najverovatnije glavne komponente brzih struja A-tipa, koji mogu biti relevantni za protok krvi majke i ploda i na taj način delovati protektivno za razvoj fetusa. Takođe, oni mogu predstavljati senzitivne pokazatelje hemodinamskih i/ili metaboličkih promena u lokalnoj fetomaternalnoj sredini.
T2  - Vojnosanitetski pregled
T1  - Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies
T1  - Ekspresija kalijumovih kanala Kv4.2 i Kv4.3 u humanim pupčanim venama zdravih trudnica, trudnica sa gestacijskim dijabetesom melitusom i trudnica sa gestacijskom hipertenzijom
VL  - 80
IS  - 1
SP  - 71
EP  - 77
DO  - 10.2298/VSP211014005D
ER  - 

@article{
author = "Đokić, Vladimir and Gostimirović, Miloš and Rajković, Jovana and Rakočević, Jelena and Labudović-Borović, Milica and Janković, Svetlana and Stanišić, Jelena and Kostić, Milan and Đurić, Miloš and Gojković-Bukarica, Ljiljana",
year = "2023",
abstract = "Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type cur-rents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collective-ly, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment., Uvod/Cilj. Značajan niz dokaza ukazuje na to da su kanali Kv4.2 i Kv4.3 glavne komponente brzih prolazno- ispravljačkih struja kalijuma (struje tipa A). Pretpostavlja se da bi te struje mogle da budu uključene u održavanje membranskog potencijala ćelije, kao i u regulaciju propagacije i učestalosti akcionih potencijala. Međutim, vrlo malo se zna o prisustvu i funkciji struje tipa A u glatkim mišićima krvnih sudova čoveka, kao što je humana umbilikalna vena (HUV). S obzirom na njenu ključnu ulogu u adekvatnoj oksigenaciji fetusa, cilj rada bio je da se utvrdi da li su podtipovi kalijumovih kanala Kv4.2 i Kv4.3 prisutni u glatkim mišićima HUV-a i da se istraže potencijalne promene njihove ekspresije tokom patoloških stanja majke – gestacijskog dijabetesa melitusa (GDM) i arterijske hipertenzije (AH) izazvane trudnoćom (AHT). Metode. U istraživanje su uključene HUV sakupljene posle trudnoće zdravih porodilja, onih čije trudnoće su bile komplikovane GDM i AH. Svaka grupa sastojala se od 6 uzoraka HUV-a dobijenih iz 6 zdravih trudnoća, 6 trudnoća komplikovanih GDM i 6 trudnoća komplikovanih AH. Nakon farmakoloških analiza, urađene su imunohistohemijska (IH) analiza i Western blot. Rezultati. Primenom IH analize pokazan je sličan obrazac ekspresije obe podjedinice Kv4.2 i Kv4.3 kanala u glatkim mišićima HUV-a u svim grupama trudnica. Rezultati dobijeni Western blot-om bili su u skladu sa IH bojenjem. Ekspresija podjedinica Kv4.2 i Kv4.3 nije se značajno razlikovala između grupa trudnica. Zaključak. Ovo je prema našim saznanjima prva studija kojom je pokazano prisustvo Kv4.2 i Kv4.3 kalijumovih kanala u glatkim mišićima HUV-a zdravih porodilja, kao i onih porodilja čija je trudnoća bila praćena prisustvom GDM ili AHT. Ti kanali su najverovatnije glavne komponente brzih struja A-tipa, koji mogu biti relevantni za protok krvi majke i ploda i na taj način delovati protektivno za razvoj fetusa. Takođe, oni mogu predstavljati senzitivne pokazatelje hemodinamskih i/ili metaboličkih promena u lokalnoj fetomaternalnoj sredini.",
journal = "Vojnosanitetski pregled",
title = "Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies, Ekspresija kalijumovih kanala Kv4.2 i Kv4.3 u humanim pupčanim venama zdravih trudnica, trudnica sa gestacijskim dijabetesom melitusom i trudnica sa gestacijskom hipertenzijom",
volume = "80",
number = "1",
pages = "71-77",
doi = "10.2298/VSP211014005D"
}

Đokić, V., Gostimirović, M., Rajković, J., Rakočević, J., Labudović-Borović, M., Janković, S., Stanišić, J., Kostić, M., Đurić, M.,& Gojković-Bukarica, L.. (2023). Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies. in Vojnosanitetski pregled, 80(1), 71-77.
https://doi.org/10.2298/VSP211014005D

Đokić V, Gostimirović M, Rajković J, Rakočević J, Labudović-Borović M, Janković S, Stanišić J, Kostić M, Đurić M, Gojković-Bukarica L. Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies. in Vojnosanitetski pregled. 2023;80(1):71-77.
doi:10.2298/VSP211014005D .

Đokić, Vladimir, Gostimirović, Miloš, Rajković, Jovana, Rakočević, Jelena, Labudović-Borović, Milica, Janković, Svetlana, Stanišić, Jelena, Kostić, Milan, Đurić, Miloš, Gojković-Bukarica, Ljiljana, "Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies" in Vojnosanitetski pregled, 80, no. 1 (2023):71-77,
https://doi.org/10.2298/VSP211014005D . .

TY  - 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 . .

TY  - JOUR
AU  - Rajković, Jovana
AU  - Perić, M.
AU  - Stanišić, Jelena
AU  - Novaković, Radmila
AU  - Đokić, Vladimir
AU  - Rakočević, Jelena T.
AU  - Tepavčević, Snežana
AU  - Labudović-Borović, Milica
AU  - Gostimirović, Miloš
AU  - Heinle, Helmut
AU  - Gojković-Bukarica, Ljiljana
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9054
AB  - Type 2 diabetes mellitus (T2DM) increases cardiovascular complications. Diabetic vascular dysfunction is associated with the reduced activity of the different smooth muscle potassium (K+) channels. Thus, the objective of our study was to investigate the role of the adenosine triphosphate (ATP)-sensitive K+ (KATP) channels in the relaxant effect of potassium channel opener, pinacidil on the human saphenous vein (HSV) obtained from the patients with and without T2DM. The rings of HSV without the endothelium, obtained from the patients who had undergone coronary bypass surgery, were mounted in an organ bath system and isometric tension was recorded. The relaxation of HSV, precontracted with phenylephrine, was produced by pinacidil. The expression of KATP subunits (Kir6.1, Kir6.2 and SUR2B) was detected by immunohistochemistry and Western blot. Pinacidil produces comparable effects on HSV in patients with and without T2DM. The suppression of pinacidil effect and its maximal relaxation by glibenclamide, selective blocker of KATP channels, was more pronounced on HSV in patients without T2DM. All three types of KATP subunits are expressed on the smooth muscle cells of HSV. While there are no differences in the expression of Kir6.1 and Kir6.2, the expression of SUR2B is lower in HSV in patients with T2DM. Pinacidil produced comparable KATP-dependent and -independent relaxation of the HSV in patients with/without T2DM. According to the effect of glibenclamide and the applied molecular analysis, presented findings demonstrated that diabetes mellitus was associated with the reduced expression of SUR2B subunit in the vascular smooth muscle of HSV.
T2  - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
T1  - The role of the adenosine triphosphate-sensitive potassium channels in pinacidil-induced vasodilatation of the human saphenous vein in patients with and without type 2 diabetes mellitus
VL  - 71
IS  - 1
DO  - 10.26402/jpp.2020.1.12
ER  - 

@article{
author = "Rajković, Jovana and Perić, M. and Stanišić, Jelena and Novaković, Radmila and Đokić, Vladimir and Rakočević, Jelena T. and Tepavčević, Snežana and Labudović-Borović, Milica and Gostimirović, Miloš and Heinle, Helmut and Gojković-Bukarica, Ljiljana",
year = "2020",
abstract = "Type 2 diabetes mellitus (T2DM) increases cardiovascular complications. Diabetic vascular dysfunction is associated with the reduced activity of the different smooth muscle potassium (K+) channels. Thus, the objective of our study was to investigate the role of the adenosine triphosphate (ATP)-sensitive K+ (KATP) channels in the relaxant effect of potassium channel opener, pinacidil on the human saphenous vein (HSV) obtained from the patients with and without T2DM. The rings of HSV without the endothelium, obtained from the patients who had undergone coronary bypass surgery, were mounted in an organ bath system and isometric tension was recorded. The relaxation of HSV, precontracted with phenylephrine, was produced by pinacidil. The expression of KATP subunits (Kir6.1, Kir6.2 and SUR2B) was detected by immunohistochemistry and Western blot. Pinacidil produces comparable effects on HSV in patients with and without T2DM. The suppression of pinacidil effect and its maximal relaxation by glibenclamide, selective blocker of KATP channels, was more pronounced on HSV in patients without T2DM. All three types of KATP subunits are expressed on the smooth muscle cells of HSV. While there are no differences in the expression of Kir6.1 and Kir6.2, the expression of SUR2B is lower in HSV in patients with T2DM. Pinacidil produced comparable KATP-dependent and -independent relaxation of the HSV in patients with/without T2DM. According to the effect of glibenclamide and the applied molecular analysis, presented findings demonstrated that diabetes mellitus was associated with the reduced expression of SUR2B subunit in the vascular smooth muscle of HSV.",
journal = "Journal of physiology and pharmacology : an official journal of the Polish Physiological Society",
title = "The role of the adenosine triphosphate-sensitive potassium channels in pinacidil-induced vasodilatation of the human saphenous vein in patients with and without type 2 diabetes mellitus",
volume = "71",
number = "1",
doi = "10.26402/jpp.2020.1.12"
}

Rajković, J., Perić, M., Stanišić, J., Novaković, R., Đokić, V., Rakočević, J. T., Tepavčević, S., Labudović-Borović, M., Gostimirović, M., Heinle, H.,& Gojković-Bukarica, L.. (2020). The role of the adenosine triphosphate-sensitive potassium channels in pinacidil-induced vasodilatation of the human saphenous vein in patients with and without type 2 diabetes mellitus. in Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 71(1).
https://doi.org/10.26402/jpp.2020.1.12

Rajković J, Perić M, Stanišić J, Novaković R, Đokić V, Rakočević JT, Tepavčević S, Labudović-Borović M, Gostimirović M, Heinle H, Gojković-Bukarica L. The role of the adenosine triphosphate-sensitive potassium channels in pinacidil-induced vasodilatation of the human saphenous vein in patients with and without type 2 diabetes mellitus. in Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2020;71(1).
doi:10.26402/jpp.2020.1.12 .

Rajković, Jovana, Perić, M., Stanišić, Jelena, Novaković, Radmila, Đokić, Vladimir, Rakočević, Jelena T., Tepavčević, Snežana, Labudović-Borović, Milica, Gostimirović, Miloš, Heinle, Helmut, Gojković-Bukarica, Ljiljana, "The role of the adenosine triphosphate-sensitive potassium channels in pinacidil-induced vasodilatation of the human saphenous vein in patients with and without type 2 diabetes mellitus" in Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 71, no. 1 (2020),
https://doi.org/10.26402/jpp.2020.1.12 . .