The Physiological Basis of Uterine Contractility: A Short Review

Wray, Susan; Kupittayanant, Sajeera; Shmygol, Anatoly; Smith, Robert; Burdyga, Theodor

doi:10.1113/eph8602114

Cited by 119 publications

(124 citation statements)

References 55 publications

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“…The search for the site and behavior of the pacemaker in the pregnant uterus has a long history (18,30,42). Several authors have suggested that the fundus of the uterus was the main origin of these contractions (2,3,8).…”

Section: Discussionmentioning

confidence: 99%

The location of pacemakers in the uteri of pregnant guinea pigs and rats

Lammers

Stephen

Al-Sultan

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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The pregnant uterus is a smooth muscle organ whose pattern of contraction is dictated by the propagation of electrical impulses. Such electrical activity may originate from one or more pacemakers, but the location of these sites has not yet been determined. To detect the location of the pacemaker in the gravid uterus, two approaches were used: 1) determine the site from where the contraction started using isolated uteri from the pregnant guinea pig, and videotape their contractions; and 2) record, in isolated uteri from pregnant term rats, with 240 extracellular electrodes simultaneously, and determine where the electrical bursts started. In both the contractile and electrophysiological experiments, there was not a single, specific pacemaker area. However, most contractions (guinea pig 87%) and bursts (rat 76%) started close to the mesometrial border (mean 2.7 ± 4.0 mm SD in guinea pigs and 1.3 ± 1.4 mm in rats). In addition, in the rat, most sites of initiations were located closer to the ovarial end of the horn (mean distance from the ovarial end 6.0 ± 6.2 mm SD), whereas such an orientation was not seen in the guinea pig. In both guinea pig and rat uteri at term, there is not one specific pacemaker area. Rather, contractile and electrical activity may arise from any site, with the majority starting close to the mesometrial border. Furthermore, in the rat, most activities started at the ovarial end of the horn. This may suggest a slightly different pattern of contraction in both species.

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Section: Discussionmentioning

confidence: 99%

The location of pacemakers in the uteri of pregnant guinea pigs and rats

Lammers

Stephen

Al-Sultan

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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show abstract

“…In the present study, the abolition of the uterotonic effect of the extract by the dihydropyridine L-type calcium channel blocker, nifedipine, suggests a possible involvement of calcium mobilization in the activity of the extract. In the rat uterus, Ca 2þ entry to the cytosol occurs almost entirely through the L-type Ca 2þ channels (Wray et al, 2001), and extract of this plant has been shown to promote the entry of extracellular calcium into the cytosol through this type of channel (Uchendu & Nwankwo, 2005).…”

Section: Discussionmentioning

confidence: 99%

Oxytocic Activity of Leaf Extract ofSpondias mombin.

Nworu¹,

Akah²,

Okoli³

et al. 2007

Pharmaceutical Biology

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The oxytocic property of leaf extract of Spondias mombin Linn. (Anacardiaceae) was evaluated in relation to its folkloric use by traditional birth attendants. The abortifacient effect of the methanol leaf extract (ME) obtained by cold maceration for 48 h, was evaluated in vivo in pregnant mice and rats at different trimesters of pregnancy. The effect of ME on isolated gravid and nongravid rat uteri preparations as well as on spontaneous contractile frequency and amplitude were investigated in vitro. The results showed that ME caused abortion in rats only in the third trimester within 24 h of administration. An effective abortifacient dose (ED 50 ) of 105.33 mg=kg was established in pregnant mice. In vitro, the extract significantly (P < 0.05) increased the amplitude and frequency of spontaneous contraction of isolated uteri preparations, which were sustained for longer periods. The uterine-stimulant effects of acetylcholine, oxytocin, ergometrine, and PGF 2a were all potentiated by ME in a dose-dependent manner. The in vivo abortifacient activity was well corroborated by the uterotonic activity of ME in vitro. Acute toxicity tests in mice revealed an intraperitoneal LD 50 of 282.44 mg=kg. Phytochemical tests showed the presence of saponins, flavonoids, tannins, glycosides, resins, protein, and triterpenes. These findings justify the use of S. mombin by traditional birth attendants in labor induction, augmentation, and as postpartum astringent.

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“…[1][2][3]. It is assumed that Ca 2ϩ entry following membrane depolarization occurs almost entirely via L-type VOCCs (31). This process is controlled by the membrane voltage and is stopped when membrane repolarization inactivates the channels.…”

Section: Description Of the Modelmentioning

confidence: 99%

Mathematical model of excitation-contraction in a uterine smooth muscle cell

Bursztyn¹,

Eytan²,

Jaffa³

et al. 2007

American Journal of Physiology-Cell Physiology

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Uterine contractility is generated by contractions of myometrial smooth muscle cells (SMCs) that compose most of the myometrial layer of the uterine wall. Calcium ion (Ca 2ϩ ) entry into the cell can be initiated by depolarization of the cell membrane. The increase in the free Ca 2ϩ concentration within the cell initiates a chain of reactions, which lead to formation of cross bridges between actin and myosin filaments, and thereby the cell contracts. During contraction the SMC shortens while it exerts forces on neighboring cells. A mathematical model of myometrial SMC contraction has been developed to study this process of excitation and contraction. The model can be used to describe the intracellular Ca 2ϩ concentration and stress produced by the cell in response to depolarization of the cell membrane. The model accounts for the operation of three Ca 2ϩ control mechanisms: voltage-operated Ca 2ϩ channels, Ca 2ϩ pumps, and Na ϩ /Ca 2ϩ exchangers. The processes of myosin light chain (MLC) phosphorylation and stress production are accounted for using the cross-bridge model of Hai and Murphy (Am J Physiol Cell Physiol 254: C99 -C106, 1988) and are coupled to the Ca 2ϩ concentration through the rate constant of myosin phosphorylation. Measurements of Ca 2ϩ , MLC phosphorylation, and force in contracting cells were used to set the model parameters and test its ability to predict the cell response to stimulation. The model has been used to reproduce results of voltage-clamp experiments performed in myometrial cells of pregnant rats as well as the results of simultaneous measurements of MLC phosphorylation and force production in human nonpregnant myometrial cells. cellular calcium control mechanisms; myometrial contractions; myosin light chain phosphorylation UTERINE CONTRACTILITY is generated by contractions of the myometrial smooth muscle cells (SMCs) that compose most of the myometrial layer of the uterine wall. In the nonpregnant uterus, synchronous contractions of these SMCs produce changes in the geometry of the uterine fluid-wall interface. These changes induce intrauterine fluid motions that are essential during early phases of reproduction (3,11,28). During parturition, the synchronized contraction of these myocytes generates the forces required to deliver the baby out of the uterus. Depolarization of the cell membrane initiates calcium ion (Ca 2ϩ ) entry into the cells through voltage-operated Ca 2ϩ channels (VOCCs) and thereby a rise in the intracellular Ca 2ϩ concentration (C Ca,i ). The elevated level of C Ca,i allows binding of Ca 2ϩ and calmodulin, thus activating myosin light-chain kinase (MLCK), which phosphorylates a regulatory myosin light chain (MLC) (29,32). This subsequently allows the formation of cross bridges between actin and myosin filaments and the generation of muscle contraction.The excitation-contraction process was studied in both rat and human myometria using the voltage-clamp technique. Stimulation of isolated myocytes using voltage pulses revealed the current-voltage relationship...

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The Physiological Basis of Uterine Contractility: A Short Review

Cited by 119 publications

References 55 publications

The location of pacemakers in the uteri of pregnant guinea pigs and rats

The location of pacemakers in the uteri of pregnant guinea pigs and rats

Oxytocic Activity of Leaf Extract ofSpondias mombin.

Mathematical model of excitation-contraction in a uterine smooth muscle cell

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