FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1530859705> ?p ?o ?g. }

• W1530859705 abstract "Chorionic plate (CPA) and stem villous (SVA) arteries located at the fetal and maternal interface of the placenta respond to stimuli including hypoxia and acidic pH which can be the result of an intermittent blood supply. Unlike other vascular tissue the placenta lacks nervous control so any response to such stimuli will be autoregulated by ion channels. Members of the two pore domain potassium channel family (K2P) the Tandem of P domains in a weak inward rectifying (TWIK) related potassium channel (TREK-1) and the TWIK Related acid sensitive K+ channel (TASK-1/3) have been shown to respond to both intracellular and extracellular pH. The hypothesis that there is differential expression and modulation of these candidate ion channels in normal pregnancy was tested. Placentae (N) were collected with written informed consent from healthy patients undergoing elective Caesarean section at term (≥37 weeks). The functional responses of resistance sized arteries (≤500µm) (n) taken from the SVA and the CPA were characterised using wire myography. Vessels were pre-contracted with U46619 and the effect of extracellular pH was studied using 1M lactic acid to produce falls of 0.2 pH units over a range of pH 7.4-6.4. The effects of a variety of ion channel modulators along with tissue oxygenation (20%, 5% and 2% O2) were also investigated on the vascular response of CPA and SVA. Western blot analysis was performed on crude CPA and SVA tissue homogenates with separation by 12% SDS-PAGE to quantify expression of TASK-1/3 and TREK-1. The subcellular localisation of each ion channel was also examined with smooth muscle cells (SMC) cultured from the CPA and SVA by confocal immunofluorescence. CPA and SVA were equally positive for TASK 1/3 (N=31) and TREK 1 (N=40) at the protein level. SMC from CPA and SVA showed expression for TASK 1/3 (N=8) with an increased fluorescence stain around the peri nuclear region. TREK-1 (N=12) expression showed a linear organisation that closely overlapped with α actin IF stain. The acidic pH stimulation triggered a biphasic relaxation that was repeated with each subsequent pH insult. A change from pH 7.4-7.2 produced a 29 ± 3% (n=9) relaxation of CPA which increased to 61 ± 4% at the lowest pH of 6.4 in 20% pO2. Similarly, altering the pH of pre-constricted SVA caused a 21 ± 2% (n=6) fall at pH 7.2 with a maximum relaxation of 69 ± 2% at pH 6.4 (p<0.01). Lowering pO2 from 20% to 5% inhibited the relaxation response seen with CPA (45 ± 3%, n=8) and SVA (34 ± 3%, n=6) at pH 6.4. CPA were also treated with the TREK-1 blocker L-methionine (1mM) which increased the relaxation to 67 ± 7% (n=6 p<0.001) at pH 6.4. Similarly the TASK 1/3 blocker ZnCl2 (1mM) gave a maximum relaxation of 72 ± 5% (n=8 p<0.01) in 20% pO2. The TREK-1 opener riluzole demonstrated a potent relaxation with both CPA (75 ± 5%, n=6) and SVA (78 ± 5%, n=6) in 20% pO2. Our data has shown that tissue oxygenation and extracellular pH within the physiological range has an important role in controlling vasodilatation in the placenta. Protons are readily transported across the cell membrane and can activate a range of targets including the K2P channels. The relaxation by riluzole has not been previously reported and implicates a direct role for TREK-1 in controlling placental vessel function. However, when TREK-1 and TASK-3 channels were blocked, the response by CPA to lower pH was exaggerated, and reflects the complex pharmacology of pH on vascular function. This also suggests that K2P channel activity can be compensated for by other pH sensitive channels and work is currently underway to identify the role of other potential ion channels that may be involved in this pathway." @default.
• W1530859705 created "2016-06-24" @default.
• W1530859705 creator A5057801157 @default.
• W1530859705 date "2012-07-16" @default.
• W1530859705 modified "2023-09-27" @default.
• W1530859705 title "Investigating the role of ion channels across the fetomaternal interface of the human placenta" @default.
• W1530859705 cites W108909600 @default.
• W1530859705 cites W119779276 @default.
• W1530859705 cites W120335510 @default.
• W1530859705 cites W125605838 @default.
• W1530859705 cites W125935861 @default.
• W1530859705 cites W138906208 @default.
• W1530859705 cites W140380104 @default.
• W1530859705 cites W1485300099 @default.
• W1530859705 cites W1500060932 @default.
• W1530859705 cites W1504796212 @default.
• W1530859705 cites W1518080919 @default.
• W1530859705 cites W1521516049 @default.
• W1530859705 cites W1534508378 @default.
• W1530859705 cites W1541419413 @default.
• W1530859705 cites W1577197696 @default.
• W1530859705 cites W1596952637 @default.
• W1530859705 cites W171819190 @default.
• W1530859705 cites W1726784060 @default.
• W1530859705 cites W1796580524 @default.
• W1530859705 cites W1854945595 @default.
• W1530859705 cites W1878890461 @default.
• W1530859705 cites W18997466 @default.
• W1530859705 cites W1901441522 @default.
• W1530859705 cites W1963631121 @default.
• W1530859705 cites W1964396898 @default.
• W1530859705 cites W1966143879 @default.
• W1530859705 cites W1966284289 @default.
• W1530859705 cites W1966420005 @default.
• W1530859705 cites W1967863888 @default.
• W1530859705 cites W1968001136 @default.
• W1530859705 cites W1970445852 @default.
• W1530859705 cites W1971022054 @default.
• W1530859705 cites W1971656740 @default.
• W1530859705 cites W1972319192 @default.
• W1530859705 cites W1972617290 @default.
• W1530859705 cites W1973272114 @default.
• W1530859705 cites W1975195151 @default.
• W1530859705 cites W1975755498 @default.
• W1530859705 cites W1976535357 @default.
• W1530859705 cites W1976827821 @default.
• W1530859705 cites W1977017927 @default.
• W1530859705 cites W1977321043 @default.
• W1530859705 cites W1978513752 @default.
• W1530859705 cites W1979071912 @default.
• W1530859705 cites W1979417846 @default.
• W1530859705 cites W1980952325 @default.
• W1530859705 cites W1981964819 @default.
• W1530859705 cites W1982213003 @default.
• W1530859705 cites W1983186128 @default.
• W1530859705 cites W1984810013 @default.
• W1530859705 cites W1986439675 @default.
• W1530859705 cites W1987245561 @default.
• W1530859705 cites W1987258233 @default.
• W1530859705 cites W1987431351 @default.
• W1530859705 cites W1988418174 @default.
• W1530859705 cites W1989074567 @default.
• W1530859705 cites W1989756791 @default.
• W1530859705 cites W1990285738 @default.
• W1530859705 cites W1990323937 @default.
• W1530859705 cites W1990445103 @default.
• W1530859705 cites W1990866037 @default.
• W1530859705 cites W1991451992 @default.
• W1530859705 cites W1991624086 @default.
• W1530859705 cites W1992900591 @default.
• W1530859705 cites W1994642596 @default.
• W1530859705 cites W1994919529 @default.
• W1530859705 cites W1996166328 @default.
• W1530859705 cites W1997080801 @default.
• W1530859705 cites W1997125695 @default.
• W1530859705 cites W1998332422 @default.
• W1530859705 cites W1998719957 @default.
• W1530859705 cites W1999723828 @default.
• W1530859705 cites W2000961219 @default.
• W1530859705 cites W2001475113 @default.
• W1530859705 cites W2002597141 @default.
• W1530859705 cites W2003263756 @default.
• W1530859705 cites W2004055816 @default.
• W1530859705 cites W2004569084 @default.
• W1530859705 cites W2004651230 @default.
• W1530859705 cites W2005791783 @default.
• W1530859705 cites W2008066000 @default.
• W1530859705 cites W2008311196 @default.
• W1530859705 cites W2010110485 @default.
• W1530859705 cites W2010371327 @default.
• W1530859705 cites W2012986942 @default.
• W1530859705 cites W2013187579 @default.
• W1530859705 cites W2015720543 @default.
• W1530859705 cites W2015865872 @default.
• W1530859705 cites W2015950622 @default.
• W1530859705 cites W2016294504 @default.
• W1530859705 cites W2016326896 @default.
• W1530859705 cites W2016511759 @default.
• W1530859705 cites W2016817628 @default.
• W1530859705 cites W2016915299 @default.

• next