Limits...
The effect of pH and ion channel modulators on human placental arteries.

Ali TY, Broughton Pipkin F, Khan RN - PLoS ONE (2014)

Bottom Line: Similarly the TASK 1/3 blocker zinc chloride (1 mM) gave a maximum relaxation of 72±5% (n = 8; p<0.01) which compared with the relaxation produced by the TREK-1 opener riluzole (75±5%; n = 6).Several other modulators induced no significant changes in vascular responses.Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Uttoxeter Road, Derby DE22 3DT, United Kingdom.

ABSTRACT
Chorionic plate arteries (CPA) are located at the maternofetal interface where they are able to respond to local metabolic changes. Unlike many other types of vasculature, the placenta lacks nervous control and requires autoregulation for controlling blood flow. The placental circulation, which is of low-resistance, may become hypoxic easily leading to fetal acidosis and fetal distress however the role of the ion channels in these circumstances is not well-understood. Active potassium channel conductances that are subject to local physicochemical modulation may serve as pathways through which such signals are transduced. The aim of this study was to investigate the modulation of CPA by pH and the channels implicated in these responses using wire myography. CPA were isolated from healthy placentae and pre-contracted with U46619 before testing the effects of extracellular pH using 1 M lactic acid over the pH range 7.4-6.4 in the presence of a variety of ion channel modulators. A change from pH 7.4 to 7.2 produced a 29±3% (n = 9) relaxation of CPA which increased to 61±4% at the lowest pH of 6.4. In vessels isolated from placentae of women with pre-eclampsia (n = 6), pH responses were attenuated. L-methionine increased the relaxation to 67±7% (n = 6; p<0.001) at pH 6.4. Similarly the TASK 1/3 blocker zinc chloride (1 mM) gave a maximum relaxation of 72±5% (n = 8; p<0.01) which compared with the relaxation produced by the TREK-1 opener riluzole (75±5%; n = 6). Several other modulators induced no significant changes in vascular responses. Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta.

Show MeSH

Related in: MedlinePlus

Immunolocalisation of placental ion channels.Cultured CPA were fixed then incubated with primary antibody to the channel of interest then visualised. Immunofluorescence for (A) TREK-1; scale bar 10 µm, (B) TASK-3; scale bar 40 µm (C) CaV1.2 channels; scale bar 10 m, was apparent. Patterns of expression varied with TREK-1 characterised by linear expression while TASK-3 was perinuclear. (D) Representative TWIK-2 expression in CPA; scale bar 10 µm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4260857&req=5

pone-0114405-g008: Immunolocalisation of placental ion channels.Cultured CPA were fixed then incubated with primary antibody to the channel of interest then visualised. Immunofluorescence for (A) TREK-1; scale bar 10 µm, (B) TASK-3; scale bar 40 µm (C) CaV1.2 channels; scale bar 10 m, was apparent. Patterns of expression varied with TREK-1 characterised by linear expression while TASK-3 was perinuclear. (D) Representative TWIK-2 expression in CPA; scale bar 10 µm.

Mentions: Protein expression and localisation of TREK-1 (n = 12; Fig. 8A) and TASK-3 (Fig. 8B) was confirmed by confocal immunofluorescence compared with control samples where primary antibody was replaced with the relevant control IgG. TREK-1 immunofluorescence was characteristically linear across the cell membrane (Fig. 8A). Representative images show TASK-3 (Fig. 8B) expression was abundant around perinuclear regions but was also membrane-associated (Fig. 8B). CaV1.2 (corresponding to LTCC) immunofluorescence was clearly observed along VSM of CPA (n = 10; Fig. 8C) and intenseTWIK-2 expression was also noted (n = 5; Fig. 8D).


The effect of pH and ion channel modulators on human placental arteries.

Ali TY, Broughton Pipkin F, Khan RN - PLoS ONE (2014)

Immunolocalisation of placental ion channels.Cultured CPA were fixed then incubated with primary antibody to the channel of interest then visualised. Immunofluorescence for (A) TREK-1; scale bar 10 µm, (B) TASK-3; scale bar 40 µm (C) CaV1.2 channels; scale bar 10 m, was apparent. Patterns of expression varied with TREK-1 characterised by linear expression while TASK-3 was perinuclear. (D) Representative TWIK-2 expression in CPA; scale bar 10 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260857&req=5

pone-0114405-g008: Immunolocalisation of placental ion channels.Cultured CPA were fixed then incubated with primary antibody to the channel of interest then visualised. Immunofluorescence for (A) TREK-1; scale bar 10 µm, (B) TASK-3; scale bar 40 µm (C) CaV1.2 channels; scale bar 10 m, was apparent. Patterns of expression varied with TREK-1 characterised by linear expression while TASK-3 was perinuclear. (D) Representative TWIK-2 expression in CPA; scale bar 10 µm.
Mentions: Protein expression and localisation of TREK-1 (n = 12; Fig. 8A) and TASK-3 (Fig. 8B) was confirmed by confocal immunofluorescence compared with control samples where primary antibody was replaced with the relevant control IgG. TREK-1 immunofluorescence was characteristically linear across the cell membrane (Fig. 8A). Representative images show TASK-3 (Fig. 8B) expression was abundant around perinuclear regions but was also membrane-associated (Fig. 8B). CaV1.2 (corresponding to LTCC) immunofluorescence was clearly observed along VSM of CPA (n = 10; Fig. 8C) and intenseTWIK-2 expression was also noted (n = 5; Fig. 8D).

Bottom Line: Similarly the TASK 1/3 blocker zinc chloride (1 mM) gave a maximum relaxation of 72±5% (n = 8; p<0.01) which compared with the relaxation produced by the TREK-1 opener riluzole (75±5%; n = 6).Several other modulators induced no significant changes in vascular responses.Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Uttoxeter Road, Derby DE22 3DT, United Kingdom.

ABSTRACT
Chorionic plate arteries (CPA) are located at the maternofetal interface where they are able to respond to local metabolic changes. Unlike many other types of vasculature, the placenta lacks nervous control and requires autoregulation for controlling blood flow. The placental circulation, which is of low-resistance, may become hypoxic easily leading to fetal acidosis and fetal distress however the role of the ion channels in these circumstances is not well-understood. Active potassium channel conductances that are subject to local physicochemical modulation may serve as pathways through which such signals are transduced. The aim of this study was to investigate the modulation of CPA by pH and the channels implicated in these responses using wire myography. CPA were isolated from healthy placentae and pre-contracted with U46619 before testing the effects of extracellular pH using 1 M lactic acid over the pH range 7.4-6.4 in the presence of a variety of ion channel modulators. A change from pH 7.4 to 7.2 produced a 29±3% (n = 9) relaxation of CPA which increased to 61±4% at the lowest pH of 6.4. In vessels isolated from placentae of women with pre-eclampsia (n = 6), pH responses were attenuated. L-methionine increased the relaxation to 67±7% (n = 6; p<0.001) at pH 6.4. Similarly the TASK 1/3 blocker zinc chloride (1 mM) gave a maximum relaxation of 72±5% (n = 8; p<0.01) which compared with the relaxation produced by the TREK-1 opener riluzole (75±5%; n = 6). Several other modulators induced no significant changes in vascular responses. Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta.

Show MeSH
Related in: MedlinePlus