Regulation of smooth muscle contraction by calcium, monomeric GTPases of the Rho subfamily and their effector kinases.

A key event in the activation of smooth muscle contraction ist the phosphorylation of the regulatory light chains of myosin (r-MLC) at Ser19 which is predominantly catalyzed by the Ca2+ and calmodulin dependent myosin light chain kinase, MLCK (Gallager et al., 1997). Recently, it has been suggested that, in addition, r-MLC phosphorylation and contraction may be induced in a Ca2+-independent manner by several protein kinases, such as Rho associated kinase, ZIP kinase, and integrin linked kinase, ILK (reviewed in Ganitkevich et al, 2002). These kinases may, hence, be involved in Ca2+-independent contractions (Kureishi et al., 1999) leading to an increased Ca2+-sensitivity of r-MLC phosphorylation and contraction. Although the physiological role of these kinases is far from clear, they may be of importance during the maintained phase of a contraction when intracellular [Ca2+] has returned to near resting values (Himpens and Somlyo, 1988; Lucius et al., 1998). One goal of this study, therefore, was to test whether Ca2+ is required for tension maintenance of an agonist induced contraction using the membrane permeant form of the caged Ca-chelator, diazo2.