Calcium signaling and uterine contractility

Abstract

Changes in Ca(2+) signals within the myometrium have important functional consequences, as they determine contractility. We show that the basic phasic nature of uterine contractions, which is essential for successful labor, is critically dependent on Ca(2+) influx through voltage-gated L-type Ca(2+) channels, and hence in turn, on membrane potential. Thus changes in ion channel expression around term will play an important role in governing uterine excitability and contractility. There remains uncertainty about which channels are present in human myometrium and the nature of the pacemaker mechanism that initiates the action potential. The sarcoplasmic reticulum may augment, to a small extent, the necessary increase in [Ca(2+)] for contraction when agonists stimulate the uterus, but its main role appears to be to control excitability, acting as a negative feedback mechanism to limit contractions. Myosin light chain kinase activity and phosphorylation of myosin are essential components in the pathway of uterine contraction, once Ca(2+) has been elevated. Modulation of myosin light chain phosphatase activity can also influence contractions, but the effects are small compared with those modulating myosin light chain kinase. Ca(2+)-sensitizing pathways may not be utilized much in modulating normal phasic uterine activity, and caution is needed in extrapolating from in vitro experiments to in vivo conditions, especially because there may be redundant pathways. There is a need to study appropriate physiologic preparations, but these are not always available (eg, preterm laboring myometrium) and to combine functional studies with modern molecular approaches, to advance our understanding to a new level, from which better therapeutics will be developed.

Uterine relaxant effects of Curcuma aeruginosa Roxb. rhizome extracts

“…Oxytocin and PGF 2␣ cause myometrium contractions by acting on oxytocin and prostaglandin FP receptors, respectively (Zingg and Laporte, 2003;Myatt and Lye, 2004;Shmygol et al, 2006) which result in the release of Ca 2+ from an intracellular store through stimulation of Gq-phospholipase C (PLC)-inositol triphosphate (IP 3 ) pathway (Phillippe et al, 1997;Asokan et al, 2002;Wray et al, 2003;Zingg and Laporte, 2003;Myatt and Lye, 2004;Shmygol et al, 2006). Besides the intracellular source, there is evidence to show that the influx of extracellular Ca 2+ provides the major increase in intracellular Ca 2+ since calcium channel blockers abolished the contractions of both agonists (Perusquia and Kubli-Garfias, 1992;Kawarabayashi et al, 1997;Phillippe et al, 1997;Sultatos, 1997;Ruttner et al, 2002).…”

<i>Dryopteris filix-mas</i> (Dryopteridaceae) leaves inhibit mouse uterine activity

“…It may therefore seem that the inhibition of the amplitude of myometrial contraction markedly observed in this study may be attributed to the prevention of MLC20 phosphorylation by DF. Activation of MLCK by CalM translocation of activated MLCK towards the contractile apparatus may be the rate-limiting step of contraction (Wray et al 2003) determining the contraction frequency of the myometrium. It would also seem that with the effect of DF being somewhat more pronounced on the amplitude than the frequency of spontaneous contractions, DF may exert less activity on MLCK activation and possibly a greater effect on prevention of MLC20 phosphorylation.…”

The Effect of Hydro-Alcoholic Extract of Rosa damascena on Uterine Constriction of Virgin Rats

“…As Sedighi et al results indicated that R. damascena Mill decreased ileum contractions induced by KCl dose-dependently probably through stimulating the β-adrenergic receptors and inhibition of voltage-dependent calcium channels in the rat (15). The basic phasic nature of uterine contraction is critically dependent on calcium influx and on membrane potential (27)(28)(29) and R. damascena may affect calcium channels. Cyclic AMP relaxant effect on uterine smooth muscle is mediated through inhibition of calcium mobilization and the contractile apparatus (30,31).…”