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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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Contractile responses recorded in response to the potassium channel blocker tetraethylammonium chloride (TEA) or an agonist (oxytocin) on cervical and vaginal smooth muscle with uterine data presented for comparative purposes.Application of TEA (10 mM) enhanced spontaneous contractions in uterine (A) and cervical (B) tissues and caused vaginal (C) and cervical tissues in diestrus and proestrus (data not shown) to become spontaneously active. Application of oxytocin (1 nM) to uterine (D), cervical (E) and vaginal (F) tissues caused a large contraction that gradually decreased revealing spontaneous contractions at high frequency for all three tissues.
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pone-0111307-g004: Contractile responses recorded in response to the potassium channel blocker tetraethylammonium chloride (TEA) or an agonist (oxytocin) on cervical and vaginal smooth muscle with uterine data presented for comparative purposes.Application of TEA (10 mM) enhanced spontaneous contractions in uterine (A) and cervical (B) tissues and caused vaginal (C) and cervical tissues in diestrus and proestrus (data not shown) to become spontaneously active. Application of oxytocin (1 nM) to uterine (D), cervical (E) and vaginal (F) tissues caused a large contraction that gradually decreased revealing spontaneous contractions at high frequency for all three tissues.

Mentions: In order to see if vaginal muscle could be induced to exhibit phasic contractions we tested the K+ channel blocker TEA and oxytocin. TEA is known to increase contractility in rat myometrial strips through increasing the excitability of smooth muscle [37] most likely by blocking voltage dependent K+ channels such as Kv7, inhibition of which has been shown to increase myometrial contractions [38]. Oxytocin, which is known to enhance spontaneous uterine contractions, induced phasic vaginal contractions. For comparison, we also tested TEA and oxytocin on the cervix and uterus. TEA increased the strength of uterine and cervical contractions (Figure 4A, B, n = 4 for both). Notably, it induced 19/22 normally quiescent vaginal tissues to exhibit strong phasic contractions of amplitude near 0.2 mN/mg tissue weight at a frequency of 7.1±1.7 per 5 min (Figure 4C; see also [39]). TEA-induced contractions were reasonably stable over the time period of our experiments, the 60/30 min frequency and amplitude ratios being 0.82±0.19 and 0.84±0.11 (n = 5) respectively. Oxytocin (1 nM) caused tonic contractions of the uterine, cervical and vaginal smooth muscles that gradually declined in amplitude with the onset of phasic contractions (Figure 4D–F; n = 5, 5 & 4 respectively).


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)

Contractile responses recorded in response to the potassium channel blocker tetraethylammonium chloride (TEA) or an agonist (oxytocin) on cervical and vaginal smooth muscle with uterine data presented for comparative purposes.Application of TEA (10 mM) enhanced spontaneous contractions in uterine (A) and cervical (B) tissues and caused vaginal (C) and cervical tissues in diestrus and proestrus (data not shown) to become spontaneously active. Application of oxytocin (1 nM) to uterine (D), cervical (E) and vaginal (F) tissues caused a large contraction that gradually decreased revealing spontaneous contractions at high frequency for all three tissues.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111307-g004: Contractile responses recorded in response to the potassium channel blocker tetraethylammonium chloride (TEA) or an agonist (oxytocin) on cervical and vaginal smooth muscle with uterine data presented for comparative purposes.Application of TEA (10 mM) enhanced spontaneous contractions in uterine (A) and cervical (B) tissues and caused vaginal (C) and cervical tissues in diestrus and proestrus (data not shown) to become spontaneously active. Application of oxytocin (1 nM) to uterine (D), cervical (E) and vaginal (F) tissues caused a large contraction that gradually decreased revealing spontaneous contractions at high frequency for all three tissues.
Mentions: In order to see if vaginal muscle could be induced to exhibit phasic contractions we tested the K+ channel blocker TEA and oxytocin. TEA is known to increase contractility in rat myometrial strips through increasing the excitability of smooth muscle [37] most likely by blocking voltage dependent K+ channels such as Kv7, inhibition of which has been shown to increase myometrial contractions [38]. Oxytocin, which is known to enhance spontaneous uterine contractions, induced phasic vaginal contractions. For comparison, we also tested TEA and oxytocin on the cervix and uterus. TEA increased the strength of uterine and cervical contractions (Figure 4A, B, n = 4 for both). Notably, it induced 19/22 normally quiescent vaginal tissues to exhibit strong phasic contractions of amplitude near 0.2 mN/mg tissue weight at a frequency of 7.1±1.7 per 5 min (Figure 4C; see also [39]). TEA-induced contractions were reasonably stable over the time period of our experiments, the 60/30 min frequency and amplitude ratios being 0.82±0.19 and 0.84±0.11 (n = 5) respectively. Oxytocin (1 nM) caused tonic contractions of the uterine, cervical and vaginal smooth muscles that gradually declined in amplitude with the onset of phasic contractions (Figure 4D–F; n = 5, 5 & 4 respectively).

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