The regulation of myosin phosphatase in pregnant human myometrium

Myometrial smooth muscle contractility is regulated predominantly through the reversible phosphorylation of MYLs (myosin light chains), catalysed by MYLK (MYL kinase) and MYLP (MYL phosphatase) activities. MYLK is activated by Ca²⁺–calmodulin, and most uterotonic agonists operate through myometrial receptors that increase [Ca²⁺]_i (intracellular Ca²⁺ concentration). Moreover, there is substantial evidence for Ca²⁺-independent inhibition of MYLP in smooth muscle, leading to generation of increased MYL phosphorylation and force for a given [Ca²⁺]_i, a phenomenon known as ‘Ca²⁺-sensitization’. ROCK (Rho-associated kinase)-mediated phosphorylation and inhibition of MYLP has been proposed as a mechanism for Ca²⁺-sensitization in smooth muscle. However, it is unclear to date whether the mechanisms that sensitize the contractile machinery to Ca²⁺ are important in the myometrium, as they appear to be in vascular and respiratory smooth muscle. In the present paper, we discuss the signalling pathways regulating MYLP activity and the involvement of ROCK in myometrial contractility, and present recent data from our laboratory which support a role for Ca²⁺-sensitization in human myometrium.