Dodds Kelsi N, Staikopoulos Vasiliki, Beckett Elizabeth A H
Discipline of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Discipline of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
Biol Reprod. 2015 Jun;92(6):141. doi: 10.1095/biolreprod.115.129809. Epub 2015 Apr 29.
Mechanisms involved in the generation of spontaneous uterine contractions are not fully understood. Kit-expressing interstitial cells of Cajal are pacemakers of contractile rhythm in other visceral organs, and recent studies describe a role for Ca(2+)-activated Cl(-) currents as the initiating conductance in these cells. The existence and role of similar specialized pacemaker cells in the nonpregnant uterus remains undetermined. Spontaneous contractility patterns were characterized throughout the estrous cycle in isolated, nonpregnant mouse uteri using spatiotemporal mapping and tension recordings. During proestrus, estrus, and diestrus, contraction origin predominated in the oviduct end of the uterus, suggesting the existence of a dominant pacemaker site. Propagation speed of contractions during estrus and diestrus were significantly slower than in proestrus and metestrus. Five major patterns of activity were predominantly exhibited in particular stages: quiescent (diestrus), high-frequency phasic (proestrus), low-frequency phasic (estrus), multivariant (metestrus), and complex. Kit-immunopositive cells reminiscent of pacemaking ICCs were not consistently observed within the uterus. Niflumic acid (10 μM), anthracene-9-carboxylic acid (0.1-1 mM), and 5-nitro-2-(3-phenylpropylamino)benzoic acid (10 μM) each reduced the frequency of spontaneous contractions, suggesting involvement of Cl(-) channels in generating spontaneous uterine motor activity. It is unlikely that this conductance is generated by the Ca(2+)-activated Cl(-) channels, anoctamin-1 and CLCA4, as immunohistochemical labeling did not reveal protein expression within muscle or pacemaker cell networks. In summary, these results suggest that spontaneous uterine contractions may be generated by a Kit-negative pacemaker cell type or uterine myocytes, likely involving the activity of a yet-unidentified Cl(-) channel.
自发子宫收缩产生的机制尚未完全明确。表达Kit的Cajal间质细胞是其他内脏器官收缩节律的起搏器，最近的研究表明，Ca(2+)激活的Cl(-)电流在这些细胞中作为起始电导发挥作用。非妊娠子宫中类似的特殊起搏器细胞的存在及其作用仍未确定。使用时空映射和张力记录，对分离的非妊娠小鼠子宫在整个发情周期中的自发收缩模式进行了表征。在发情前期、发情期和间情期，收缩起源主要在子宫的输卵管端，提示存在一个主要的起搏器部位。发情期和间情期收缩的传播速度明显慢于发情前期和发情后期。在特定阶段主要表现出五种主要的活动模式：静止（间情期）、高频相性（发情前期）、低频相性（发情期）、多变量（发情后期）和复杂模式。在子宫内未始终观察到类似起搏ICC的Kit免疫阳性细胞。尼氟灭酸（10 μM）、蒽-9-羧酸（0.1 - 1 mM）和5-硝基-2-(3-苯丙基氨基)苯甲酸（10 μM）均降低了自发收缩的频率，提示Cl(-)通道参与了子宫自发运动活动的产生。这种电导不太可能由Ca(2+)激活的Cl(-)通道、anoctamin-1和CLCA4产生，因为免疫组织化学标记未显示在肌肉或起搏器细胞网络中有蛋白表达。总之，这些结果表明，自发子宫收缩可能由Kit阴性的起搏器细胞类型或子宫肌细胞产生，可能涉及一种尚未确定的Cl(-)通道的活动。
