Smooth muscle activation

Calcium-dependent regulation involves the calcium-calmodulin complex that activates smooth muscle MLCK, a monomer of approximately 135 kDa. Dephosphorylation is initiated by MLCP. MLCP is a complex of three proteins a 110-130 kDa myosin phosphatase targeting and regulatory subunit (MYPT1), a 37 kDa catalytic subunit (PP-1C) and a 20 kDa subunit of unknown function. In most cases, calcium-independent regulation of smooth muscle tone is achieved by inhibition of MLCP activity at constant calcium level inducing an increase in phospho-rMLC and contraction (Fig. 1). 

However, it is clear that the resting compliance is relatively more important to the springlike behavior of many active smooth muscles. Each smooth muscle must be analyzed individually since the extracellular compartment of each smooth muscle as a histological entity is different. 

When smooth muscle myosin is bound to F-actin in the absence of other muscle proteins such as tropomyosin, there is no detectable ATPase activity. This absence of activity is quite unlike the situation described for striated muscle myosin and F-actin, which has abundant ATPase activity. Smooth muscle myosin contains fight chains that prevent the binding of the myosin head to F-actin they must be phosphorylated before they allow F-actin to activate myosin ATPase. The ATPase activity then attained hydrolyzes ATP about tenfold more slowly than the corresponding activity in skeletal muscle. The phosphate on the myosin fight chains may form a chelate with the Ca bound to the tropomyosin-TpC-actin complex, leading to an increased rate of formation of cross-bridges between the myosin heads and actin. The phosphorylation of fight chains initiates the attachment-detachment contraction cycle of smooth muscle. 

Dick GM, Hunter AC, Sanders KM (2002) Ethylbromide tamoxifen, a membrane-impermeant antiestrogen, activates smooth muscle calcium-activated large-conductance potassium channels from the extracellular side. Mol Pharmacol 61 (5) 1105—1113... 

Dick GM, Rossow CF, Smirnov S, Horowitz B, Sanders KM (2001) Tamoxifen activates smooth muscle BK channels through the regulatory beta 1 subunit. J Biol Chem 276 34594-34599... 

Blaustein This is not smooth muscle it is using cultured cells. In relation to the previous discussion, does this have any relevance to real life Are you doing the comparison to look at the role of PLC in activating smooth muscle Clearly, you have shown that Ca2+ modulation of the L1SP3 receptor has profound effects. Relative to this, how about the effects of Ca2+ on the PLC cascade ... 

Toeroek, K. Cowley, D.J. Brandmeier, B.D. Howell, S. Aitken, A. Tren-tham, D.R. Inhibition of calmodulin-activated smooth-muscle myosin light-chain kinase by calmodulin-binding peptides and fluorescent (phosphodiesterase-activating) calmodulin derivatives. Biochemistry, 37, 6188-6198 (1998)... 

Nitric oxide Cyclase activation, smooth muscle relaxation Nitric oxide synthase... 

Smooth muscles are not regulated by the troponin system. Rather it is the phosphorylation of the myosin light chains which appears to be the event which activates smooth muscle contraction. 

Figure 16.23 Pharmacological setup for isometric tension (contractility) recordings of isolated smooth muscle preparations under the influence of ion channel modulators (inhibitors and activators). Smooth muscle strips (as visible on the second enlarged picture) or rings are placed in thermostatically controlled tissue baths and are connected to a force displacement transducer for isometric recording. The force signal (contractions) is recorded electronically via specialized software and displayed on a monitor.

The importance of Ser-19 phosphorylation for actin-activated smooth muscle myosin MgATPase activity and for contraction of smooth muscle stimulated research to find out which amino acids, surrounding the serine, are required for the phosphorylation. Using synthetic peptide analogs of the native phosphorylation site comprising residues from Lys-11 to Ala-23, it was shown that Arg-16 had a strong influence on the kinetics of peptide phosphorylation (Kemp and Pearson, 1985). The location of Arg-16 in relation to Ser-19, as well as the distance between Arg-13 and Arg-16, was found to be important. Placement of Arg-16 at position 15 caused a complete switch in specificity from the natural Ser-19 phosphorylation site to Thr-18. Increasing the number of alanine residues between Arg-13 and Arg-16 in the model peptide also influenced the kinetics and site specificity of peptide phosphorylation. On the carboxyl side of Ser-19, Val-21 and Phe-22 influenced the of peptide phosphorylation, whereas Ala-23 was found not to be essential (Pearson et ah, 1986). 

Depression of the force-RLC phosphorylation relation in intact smooth muscle was first described by Gerthoffer (1987), who demonstrated that elevating RLC phosphorylation by readdition of external Ca + in the presence of agonist was not accompanied by force development. Subsequently, others have shown depression of the force-RLC phosphorylation relation upon relaxation of activated smooth muscle with low concentrations of the phosphatase inhibitor okadaic acid or high external [Mg +] (Tansey et al., 1990 D Angelo etal., 1992, respectively, and Chapter 25, this volume). In these studies, relaxation was accompanied by... 

When activated smooth muscle is allowed to shorten isotonically, the rate of shortening decreases continuously during the period of shortening until an equilibrium length is reached. This phenomenon is widely observed among different smooth muscle tissues, and occurs in single... 

Simons M, Leclerc G, Safian RD, Isner JM, Weir L, Bairn DS (1993) Relation between activated smooth-muscle cells in coronary artery lesions and restenosis after atherectomy. N Engl J Med 328 608-613... 

Endothelins are much more potent than norepinephrine as vasoconstrictors and have a relatively long-lasting effect. The peptides also stimulate the heart, increase atrial natriuretic peptide release, and activate smooth muscle proliferation. The peptides may be involved in some forms of hypertension and other cardiovascular disorders. Antagonists have recently become available for research use. 

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