Myosin light chains cycling

These messengers also play a role in regulating contraction of myometrium, which consists of smooth muscle fibres. Contraction is controlled by increases in the concentration of cytosolic Ca ions. Prostaglandins activate Ca ion channels in the plasma membrane of the fibres oxytocin activates release of Ca from intracellular stores. The increase in concentration of Ca ions leads to activation of myosin light-chain kinase which leads to crossbridge cycling and contraction (as described in Chapter 22 Figure 22.12). 

Figure 22.12 Regulation of actin-myosin interaction in smooth muscle via the light-chain kinase and phosphatase and effect on blood pressure. ions bind to calmodulin and the complex stimulates the conversion of inactive myosin light chain kinase (MLCK) to active MLCK which then phosphorylates the light chain. This results in activation of the cross-bridge cycle. The overall effect is vasoconstriction of the arteriole, which increases blood pressure.

Fig. 4. The temporal sequence of events when a resting strip of tracheal smooth muscle is activated by carbacholamine addition at 10 min. There is a transient rise in [Ca2+]c (—) followed by a transient increase in the content (—) of phosphorylated myosin light chains (MLC-P) which lead in turn to the initiation of force development (—). Increased force is sustained even though the content of MLC-P declines. Preceding the sustained phase of force maintenance, there is an increase in the phosphorylation of desmin (D-P), synemin (S-P), caldesmon (CD-P) and a number of low molecular weight cytosolic proteins (X-P). These remain phosphorylated throughout the sustained phase of the response during which there is a sustained increase in Ca2+ cycling across the plasma membrane which regulates the activity of the membrane-associated protein kinase C.

The more classic pathway of smooth muscle contractile activation is illustrated in the right-hand side of this panel, where activation leads to an increase in intracellular ionized calcium concentration ([Ca +jj) by virtue of Ca + entry through channels or exchangers (Lyu et al, 1992 van Breemen et al, 1985 Khalil et al, 1987) or the release of Ca2+ from the sarcoplasmic reticulum. [Ca +J in combination with calmodulin activates myosin light chain (MLC) kinase to cause phosphorylation of the 20-kDa MLC, which in turn results in increased actin-activated myosin AT-Pase activity, increase cross-bridge cycling velocity, and, as a result, an increase in contractile force (Aksoy et al, 1976 Sobieszek, 1977). 

Murphy RA, Aksoy MO, Dillon PF, Gerthoffer WT, Kamm KE (1983) The role of myosin light chain phosphorylation in regulation of the cross-bridge cycle. Fed Proc 42 51-56... 

Wingard CJ, Paul RJ, Murphy RA (1997) Energetic cost of activation processes during contraction of swine arterial smooth muscle. J Physiol (Lond) 501 213-223 Word RA, Tang DC, Kamm KE (1994) Activation properties of myosin light chain kinase during contraction/relaxation cycles of tonic and phasic smooth muscles. J Biol Chem 269 21596-21602... 

The calmodulin-4Ca +-activated light chain kinase phosphorylates the hght chains, which then ceases to inhibit the myosin-F-actin intetaction. The contraction cycle then begins. 

Regulation by myosin phosphorylation, which is of particular importance for smooth muscle, is a feature of the less specialized actomyosin contractile systems. In striated muscle it would appear that light chain phosphorylation has been relegated to a modulatory role in the cross-bridge cycle, and response to stimulation has been accelerated by the evolution of the troponin system located in the I filament. The consequence is that the rapid binding of calcium to one molecule of troponin C renders seven actin molecules available to interact with as many heads of myosin molecules as they can accommodate. In smooth muscle, binding of cal-... 

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