Calcium myosin phosphorylation, other

Cytoplasmic calcium concentration phosphorylation of myosin light chains and (less important) other proteins interactions with actin-binding proteins. 

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The major relaxing transmitters are those that elevate the cAMP or cGMP concentration (Fig. 3). Adenosine stimulates the activity of cAMP kinase. The next step is not clear, but evidence has been accumulated that cAMP kinase decreases the calcium sensitivity of the contractile machinery. In vitro, cAMP kinase phosphorylated MLCK and decreased thereby the affinity of MLCK for calcium-calmodulin. However, this regulation does not occur in intact smooth muscle. Possible other substrate candidates for cAMP kinase are the heat stable protein HSP 20, (A heat stable protein of 20 kDa that is phosphorylated by cGMP kinase. It has been postulated that phospho-HSP 20 interferes with the interaction between actin and myosin allowing thereby smooth muscle relaxation without dephosphorylation of the rMLC.) Rho A and MLCP that are phosphorylated also by cGMP kinase I (Fig. 3). 

Once the intracellular Ca " concentration begins to rise, calmodulin-calcium binding also rises and MLCK, which is dependent on calmodulin activation, rises in turn. The next step in this cascade is the phosphorylation of myosin. Finally, the phosphorylation of myosin results in the activation of the crossbridges and the accompanying transduction of ATP energy into mechanical work. Despite its differences in regulation, smooth muscle behaves mechanically much like other muscles. 

Apart from the phosphorylation theory, other regulatory mechanisms have also been suggested for smooth muscle contraction. A thin-filament protein that has been proposed as a regulatory component is caldesmon [102], Purified caldesmon is a potent inhibitor of actin-tropomyosin interaction with myosin. The mechanisms by which calcium removes this inhibition are controversial. Furthermore, phosphorylation of caldesmon by a caldesmon kinase in vitro has also been implicated in this... 

The main target of cAMP is protein kinase A (PKA) which phosphorylates various proteins on Ser and Thr residues, for instance myosin light chain kinase in smooth muscles, or Cayl calcium channels in cardiac contractile cells. Beside PKA, cAMP can also bind to some other direct targets such as HCN cationic non-selective channels in cardiac pacemaker cells (see above). 

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