Abstract
Background/AimsThe 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 FindingsVaginal 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/SignificanceCervical 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.
Highlights
The female reproductive tract (FRT) is comprised of a series of embryologically related, yet specialized organs that coordinate sexual activity, conception, fetal growth and parturition
Motility along the length of the FRT is coordinated by a combination of phasic contractile activity and nervous control, all strongly influenced by hormones
Cells immunoreactive for cKit and vimentin have been found in the uterus and human vagina [7,8] leading to speculation that pacemaking in the FRT is driven by similar mechanisms to that in the gut [9]
Summary
The female reproductive tract (FRT) is comprised of a series of embryologically related, yet specialized organs that coordinate sexual activity, conception, fetal growth and parturition. Many of these functions depend on the coordinated contraction of smooth muscle. Motility along the length of the FRT is coordinated by a combination of phasic contractile activity and nervous control, all strongly influenced by hormones. It is widely established that pacemaking in the gastrointestinal tract is driven by interstitial cells of Cajal (ICCs). These form extensive networks within the gut wall where they are strongly electrically coupled to each other and to smooth muscle. Cells immunoreactive for cKit and vimentin have been found in the uterus and human vagina [7,8] leading to speculation that pacemaking in the FRT is driven by similar mechanisms to that in the gut [9]
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