In vitro studies of animal and human myometrium have greatly increased our understanding of uterine physiology and, in particular, of the mechanisms governing excitation-contraction coupling. It is still the case, however, that much remains to be elucidated concerning how uterine contractions are controlled, especially in pre-term labours. Knock-out mice are adding to our knowledge. However, there is little background information about mouse myometrium, especially concerning contractility, ion channels and the sarcoplasmic reticulum (SR). Thus, the aim of this work was to investigate these aspects of excitation-contraction coupling.

CD-1 mice were killed humanely under CO₂ anaesthesia, and the uterus removed. Small strips were loaded with the fluorescent Ca²⁺ indicator, indo-1. The SR was inhibited using cyclopiazonic acid (CPA, 10 µM).

Mouse myometrium produced regular, phasic contractions preceded by intracellular Ca²⁺ transients (n = 20). There was no spontaneous activity in the absence of extracellular Ca²⁺, and baseline Ca²⁺ decreased (n = 16). Oxytocin, carbachol and high-K⁺ depolarising solution all increased the Ca²⁺ signal and contractions (n = 8, 4 and 6 respectively). In zero Ca²⁺, oxytocin produced a small increase in Ca²⁺ and force (n = 6). Inhibition of the SR by CPA significantly increased the frequency of contractions (n = 8). Baseline calcium was also increased. To investigate the mechanism whereby depletion of the SR Ca²⁺ increases force, we inhibited the Ca²⁺-activated ion channels. Application of the K⁺ channel inhibitors tetraethylammonium or iberiotoxin significantly increased the frequency and amplitude of contractions (n = 3). Niflumic acid, a Cl^– channel blocker, abolished spontaneous contractions (n = 5).

We concluded that these data suggest the presence of both Ca²⁺-activated K⁺ and Cl^– channels and therefore Ca²⁺ released from the SR may activate them. Given the finding of increased contractility when the SR was emptied, the current data suggest that K⁺ plays the dominant role. The SR also has an IP₃-releasable store, but its contribution to agonist-induced force production appears to be limited.