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Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy.

Gravina FS, van Helden DF, Kerr KP, de Oliveira RB, Jobling P - PLoS ONE (2014)

Bottom Line: ICs were found in small numbers in the mouse cervix but not in the vagina.Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active.Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, The University of Newcastle, Callaghan, NSW, Australia.

ABSTRACT

Background/aims: The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking.

Methodology/principal findings: Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina.

Conclusions/significance: Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

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Spontaneous contractions occur in the presence of CPA, an inhibitor of SR Ca2+ stores.Shown are the effects of inhibiting the SERCA using 10 µM CPA on contractions in uterine (A, A1), cervical (B, B1) and vaginal (C, C1) smooth muscle strips from non-prenant and pregnant mice. Recordings from vaginal tissues were made in the presence of TEA (10 mM) to reveal contractions. CPA (10 µM) applied for at least 30 minutes modulated but did not abolish the contractions in any of the three tissue types.
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pone-0111307-g006: Spontaneous contractions occur in the presence of CPA, an inhibitor of SR Ca2+ stores.Shown are the effects of inhibiting the SERCA using 10 µM CPA on contractions in uterine (A, A1), cervical (B, B1) and vaginal (C, C1) smooth muscle strips from non-prenant and pregnant mice. Recordings from vaginal tissues were made in the presence of TEA (10 mM) to reveal contractions. CPA (10 µM) applied for at least 30 minutes modulated but did not abolish the contractions in any of the three tissue types.

Mentions: The effect of the SERCA inhibitor CPA (10 µM) on spontaneous cervical and 10 mM TEA-induced phasic vaginal contractions was investigated. CPA caused a 2-fold increase in cervical contraction frequency in tissues from non-pregnant mice (4.5±0.9 vs. 2.1±1.0 contractions/5 min, n = 4, P<0.05) but did not significantly alter cervical contraction frequency in tissues from pregnant mice (n = 5). CPA did not significantly alter the TEA-induced vaginal contraction frequency in tissues from non-pregnant and pregnant mice (n = 4 & 5 respectively). CPA did not cause a significant increase in tone in these tissues. By comparison and as is known [13], [14], [15], [16], [39], application of CPA to uterine tissues from non-pregnant and pregnant mice caused an increase in resting tone and contraction frequency especially during the period shortly after application (Fig. 6A; n = 4). Notably, uterine contractions persisted during CPA application in tissues from non-pregnant mice but were abolished in uteri from pregnant mice (Fig. 6A1; n = 5).


Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy.

Gravina FS, van Helden DF, Kerr KP, de Oliveira RB, Jobling P - PLoS ONE (2014)

Spontaneous contractions occur in the presence of CPA, an inhibitor of SR Ca2+ stores.Shown are the effects of inhibiting the SERCA using 10 µM CPA on contractions in uterine (A, A1), cervical (B, B1) and vaginal (C, C1) smooth muscle strips from non-prenant and pregnant mice. Recordings from vaginal tissues were made in the presence of TEA (10 mM) to reveal contractions. CPA (10 µM) applied for at least 30 minutes modulated but did not abolish the contractions in any of the three tissue types.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206458&req=5

pone-0111307-g006: Spontaneous contractions occur in the presence of CPA, an inhibitor of SR Ca2+ stores.Shown are the effects of inhibiting the SERCA using 10 µM CPA on contractions in uterine (A, A1), cervical (B, B1) and vaginal (C, C1) smooth muscle strips from non-prenant and pregnant mice. Recordings from vaginal tissues were made in the presence of TEA (10 mM) to reveal contractions. CPA (10 µM) applied for at least 30 minutes modulated but did not abolish the contractions in any of the three tissue types.
Mentions: The effect of the SERCA inhibitor CPA (10 µM) on spontaneous cervical and 10 mM TEA-induced phasic vaginal contractions was investigated. CPA caused a 2-fold increase in cervical contraction frequency in tissues from non-pregnant mice (4.5±0.9 vs. 2.1±1.0 contractions/5 min, n = 4, P<0.05) but did not significantly alter cervical contraction frequency in tissues from pregnant mice (n = 5). CPA did not significantly alter the TEA-induced vaginal contraction frequency in tissues from non-pregnant and pregnant mice (n = 4 & 5 respectively). CPA did not cause a significant increase in tone in these tissues. By comparison and as is known [13], [14], [15], [16], [39], application of CPA to uterine tissues from non-pregnant and pregnant mice caused an increase in resting tone and contraction frequency especially during the period shortly after application (Fig. 6A; n = 4). Notably, uterine contractions persisted during CPA application in tissues from non-pregnant mice but were abolished in uteri from pregnant mice (Fig. 6A1; n = 5).

Bottom Line: ICs were found in small numbers in the mouse cervix but not in the vagina.Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active.Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical Sciences & Pharmacy, Faculty of Health & Medicine, The University of Newcastle, Callaghan, NSW, Australia.

ABSTRACT

Background/aims: The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking.

Methodology/principal findings: Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina.

Conclusions/significance: Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

Show MeSH
Related in: MedlinePlus