Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.579322
Title: The effects of prostaglandin F2α on the force/calcium relationship in pregnant rat myometrium
Author: Noble, Debbie
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2012
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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.
Supervisor: Burdyga, Theodor; Wray, Susan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.579322  DOI: Not available
Keywords: QP Physiology
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