Noble, Debbie
The effects of prostaglandin F2α on the force / calcium relationship in pregnant rat myometrium.
Doctor of Philosophy thesis, University of Liverpool.
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Abstract
Prostaglandin F2α (PGF2α) is a myometrial stimulant, both PGF2α and its receptor are reported to increase towards parturition. With high PGF2α levels correlating with pre-term birth, especially those caused by infection. The mechanism by which PGF2α exerts its affects on uterine excitation-contraction coupling is unknown. The aim of this work was to describe the relationship between force and [Ca2+]i in pregnant rat myometrium and the effects of PGF2α on this relationship. The mechanism by which PGF2α exerts its affects was also investigated, focused on the role of Ca2+ entry mechanisms. PGF2α was examined on both longitudinal strips and isolated myocytes from pregnant Wistar rats. Strips were loaded with the Ca2+ sensitive indicator Indo-1AM and simultaneous recording of [Ca2+]i and force were made using a photometric system combined with force measurements, at a sampling rate of 1KHz to get good temporal resolution. Cells were isolated using Liberase Blendzyme 3, loaded with Fluo-4AM, and [Ca2+]i recorded using a Nipkow Disk based confocal imaging system. Pregnant myometrial tissue gave three contractility patterns in control conditions; two spontaneously active, giving either irregular contractions, or smooth phasic contractions, while the third was not spontaneously active but responsive to high-K+ stimulation. All contractions were preceded by a rise in [Ca2+]i which was dependent upon Ca2+ entry through VOCC, while synchronisation was dependent upon gap junctions. PGF2α increased myometrial contractility. In spontaneous tissue there were two responses; firstly an increase in amplitude, duration and frequency of phasic contraction while the second resulted in a tonic-like contraction which lasted for the duration of agonist application. On quiescent tissue, PGF2α resulted in the imitation of spontaneous activity, which ceased upon removal of the agonist. [Ca2+]i mirrored force in respect to frequency and duration, but PGF2α did not increase the amplitude of Ca2+ transient above that seen under normal spontaneous activity. The increase in amplitude of force induced by PGF2α is caused by an increase in the frequency of Ca2+ spikes within the Ca2+ spike burst. PGF2α resulted in the oscillatory release of Ca2+ from the SR in the form of propagating Ca2+ waves, initiated at one end of the cell. Re-admission of external Ca2+ resulted in activation of a nifedipine-resistance Ca2+ influx sensitive to La3+, which suggests that the stimulant action of PGF2α is associated with activation of a Ca2+-release Ca2+-entry coupling mechanism leading to opening of a SOCE pathway. In addition to this PGF2α increase both force and [Ca2+]i when applied in the presence of CPA and nifedipine, suggesting that PGF2α also works in part through a receptor operated and / or non-selective cation channels.
| Item Type: | Thesis (Doctor of Philosophy) |
|---|---|
| Additional Information: | Date: 2012-09 (completed) |
| Subjects: | ?? QP ?? |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 30 Aug 2013 15:01 |
| Last Modified: | 16 Dec 2022 04:38 |
| DOI: | 10.17638/00010153 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/10153 |
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