Crossbridges regulation

For the purpose of discussion, crossbridge regulation can be split into three overlapping sets of reactions (a) the Ca-calmodulin cascade (MLCK activation), (b) the phosphorylation-dephosphorylation cycle (the Four State Model), and (c) actin-myosin cycle (chemomechanical transduction). 

Murphy RA (1982) Myosin phosphorylation and crossbridge regulation in arterial smooth muscle. State-of-the-art review. Hypertension 4 3-7 Murphy RA (1989) Contraction in smooth muscle cells. Annu Rev Physiol 51 275-283 Murphy RA (1994) What is special about smooth muscle The significance of covalent crossbridge regulation. FASEB J 8 311-318... 

Although in in vivo circumstances an intracellular free calcium increase apparently acts as the primary modulator of contraction, it can be bypassed in highly permeabilized smooth muscle preparations where the active subunit of MLCK can be introduced to phosphorylate myosin and induce contraction. The MLCK catalyzed phosphorylation of serine-19 is seen as the necessary event in the activation of smooth muscle myosin to form crossbridges. Thus, the rising phase of force during an isometric smooth muscle contraction follows an increase in the degree of phosphorylation of myosin, and that in turn follows the transient rise of (a) cytosolic free Ca, (b) Ca-calmodulin complexes, and (c) the active form of MLCK. The regulation of the intracellular calcium is discussed below. The dynam-... 

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. 

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). 

Hai CM, Murphy RA (1992) Adenosine 5 -triphosphate consumption by smooth muscle as predicted by the coupled four-state crossbridge model. Biophys J 61 530-541 Harris DE, Warshaw DM (1993) Smooth and skeletal muscle actin are mechanically indistinguishable in the in vitro motility assay. Circ Res 72 219-224 Hartshorne DJ, Mrwa U (1982) Regulation of smooth muscle actomyosin. Blood V essels 19 1-18... 

Nishimura J, van Breemen C (1989) Direct regulation of smooth muscle contractile elements by second messengers. Biochem Biophys Res Commun 163 929-935 Nishimura J, Kolber M, van Breemen C (1988) Norepinephrine and GTP-y-S increase myofilament Ca " sensitivity in a-toxin permeabilized arterial smooth muscle. Biochem Biophys Res Commun 157 677-683 Nishiye E, Somlyo AV, Torok K, Somlyo AP (1993) The effects of MgADP on crossbridge kinetics a laser flash photolysis study of guinea-pig smooth muscle. J Physiol (Lond) 460 247-271... 

Winder SJ, Walsh MP (1990) Smooth muscle calponin. Inhibition of actomyosin MgATPase and regulation by phosphorylation. J Biol Chem 265 10148-10155 Winder SJ, Walsh MP (1993) Calponin thin filament-linked regulation of smooth muscle contraction. Cell Signal 5 677-686 Winder SJ, Walsh MP (1996) Calponin. Curr Top Cell Regul 1996 34 33-61 Wingard CJ, Paul RJ, Murphy RA (1994) Dependence of ATP consumption on crossbridge phosphorylation in swine carotid smooth muscle. J Physiol (Lond) 481 111-117... 

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