Role of the sarcoplasmic reticulum in uterine smooth muscle.
The sarcoplasmic reticulum (SR) is present as an extensive network in uterine cells. In this chapter we examine its functional importance, relating in particular, to the control of contractility in pregnancy. The uterine SR has both ryanodine receptors (RyR) and inositol-1 ,4,5-trisphosphate InsP3 receptors (InsP3R). The RyR and subsequent Ca24-induced Ca2+ release play little role in either human or rat contractions or Ca2+ transients. There may be subtle, spatiotemporal effects at the single cell level. Caffeine, an agonist for RyR fails to release Ca2+ and indeed produces relaxation not contraction. InsP3 dearly causes release of Ca2+ from the uterine SR and an increase in force, although these changes are only small and transient compared to those occurring due to external Ca2+ entry. Inhibition of the SR Ca-ATPase by cyclopiazonic acid, empties Ca2+ from the SR. This is associated with an augmentation of force and Ca2+ transient. Thus the SR normally functions in the uterus to limit, not increase contractions. The mechanism may involve vectoral release of Ca2+ from the SR and activation of surface membrane K+ channels. This activation would tend to decrease L-type Ca2+ entry and hence reduce contraction. Thus the SR is playing a role in controlling membrane excitability and hence contractility. The SR also plays a role in the relaxation of force. This is not primarily due to a direct sequestering of large amounts of Ca2+, but rather that the SR directs Ca2+ to the surface membrane extrusion mechanisms, i.e. Ca-ATPase and Na+/Ca2+ exchanger. This enables them to act more efficiently, and therefore aids relaxation. Recent direct measurements of SR luminal content show decreases with agonist application but not during spontaneous activity; confirming the results described above. This technique will be used to better characterize the uterine SR, its control and relevance to normal and abnormal labours.
Wray
Susan
S
Department of Physiology, The University of Liverpool, UK.
Kupittayanant
Sajeera
S
Shmigol
Tony
T
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D005260:Female; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D014590:Uterine Contraction / Q000502:physiology*; D014599:Uterus / Q000166:cytology / Q000502:physiology*
D000252:Calcium-Transporting ATPases