Characterization of contractile activity and intracellular Ca2+ signalling in mouse myometrium.
OBJECTIVE
To characterize the contractile responses of mouse myometrium, the associated calcium (Ca2+) changes and the role of the sarcoplasmic reticulum (SR), and to better understand excitation contraction coupling in this tissue.


METHODS
Strips of longitudinal myometrium were used, and Ca2+ was measured after loading with Indo-1.


RESULTS
Intracellular Ca2+ transients, produced by Ca2+ entry, preceded phasic spontaneous contractions. Depolarization with high potassium concentration significantly increased the amplitude of the contractions and transformed the pattern of activity from phasic to tonic, with accompanying changes in intracellular Ca2+ concentration ([Ca2+]i). Oxytocin significantly stimulated contractile activity and [Ca2+]i above the level occurring spontaneously. Thus all forms of contractile activity were closely correlated with Ca2+. When the SR was emptied using a blocker of the SR calcium-adenosinetriphosphatase, cyclopiazonic acid, spontaneous Ca2+ and force transients increased greatly in frequency and amplitude. Ryanodine, a blocker of Ca(2+)-induced Ca2+ release (CICR), did not impair activity. In the absence of external Ca2+, oxytocin was able to release Ca2+ from the SR through IP3 but produced only a small increase in force, demonstrating a requirement for Ca2+ entry as part of the mechanism of agonist action.


CONCLUSIONS
Mouse myometrium, (1) produces contractile activity reflecting changes in [Ca2+]i irrespective of the stimulus, (2) has a significant SR Ca2+ content releasable by agonists but not CICR, (3) has an SR acting to inhibit spontaneous activity, and (4) behaves qualitatively similarly to human and rat myometrium in major aspects of excitation contraction coupling and is therefore a useful model tissue.
Matthew
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A
Department of Physiology, The University of Liverpool, United Kingdom.
Kupittayanant
S
S
Burdyga
T
T
Wray
S
S
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D009215:Myometrium / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D007211:Indoles; D012433:Ryanodine; D010121:Oxytocin; D000252:Calcium-Transporting ATPases; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid