Smooth muscle contractile activity

List the factors that may alter smooth muscle contractile activity... 

All of these factors (ANS stimulation, blood-borne and locally produced substances) alter smooth muscle contractile activity by altering the intracellular concentration of calcium. An increase in cytosolic calcium leads to an increase in crossbridge cycling and therefore an increase in tension... 

Taggart MJ, Wray S 1998 Contribution of sarcoplasmic reticular calcium to smooth muscle contractile activation gestational dependence in isolated rat uterus. J Physiol 511 133—144... 

Nicholls and Skidmore (65) demonstrated that dust collected from mills with a higher prevalence of byssinosis caused greater smooth muscle contractile activity than dust from mills with a lower prevalence. Recently, Russell e al. (66) used an isolated tissue bath to measure canine trachealis muscle contraction caused by cotton bract extracts (CBE). Morey et al. (67) showed that cotton bract represents 20-43% of the cotton dust total thus, the findings of Paton and Davenport using cotton dust agree in principle with Russell e al., who used cotton bract. Davenport and Paton (62) found a percentage of the activity of CDE represented by a 5HT-like component, but they also found at least one more active substance in the CDE than Russell et al. (66). 

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). 

Smooth muscle cell activity is in general under neural control. Thus, the many transmitters of the autonomic nervous system are paired with receptors on the smooth muscle cell membrane. One of the current questions about smooth muscle function is What intracellular processes are the different transmitters modulating in the smooth muscle cells, in addition to their effects on the contractile state ... 

Herrera MD, Zarzuelo A, Jimenez J, Marhuenda E, Duarte J. 1996. Effects of flavonoids on rat aortic smooth muscle contractility structure-activity relationships. Gen Pharmacol 27 273-277. 

Holton My understanding is that the vena cava is a tonic smooth muscle, and therefore it is right at one end of a spectrum of smooth muscle contractile types. This means that, it generates tension slowly, it maintains tension when it is activated and it doesn t show action potentials. Its organization may be very different from a phasic smooth muscle that normally operates by action potentials and cannot maintain tension. 

Relative activities are from Cushman and Ondetti (72). The activity of each peptide to increase the smooth muscle contractile action of bradykinin was determined relative to SQ20,881 (100%). 

Based on this, one would predict that treatment of intact smooth muscle preparations with an inhibitor of CaMKII should potentiate myosin light chain phosphorylation and the rapid phase of force development. In contrast, we have found that in carotid arterial smooth muscle, KN-93 inhibition of CaMKII activation in response to physiological contractile stimuli correlates with a marked inhibition of tonic force responses (Rokolya and Singer 2000), suggesting an alternative dominant action of CaMKII on the smooth muscle contractile apparatus. 

In smooth muscle, P-adrenoceptors decrease contractility PKA phosphorylates MLCK, which thereby becomes inactivated. In contrast, aj-adrenoceptors increase smooth muscle contractility. They activate phospholipase C, which in turn releases inositoltriphosphate (IP3) from the endoplasmic reticulum by binding to a cognate receptor channel (Figure 6.10c). Ca then binds to calmodulin, which in turn activates myosin light chain kinase. 

These two phenotypes of smooth muscle, in addition to having marked differences in contractile activity, express different isoforms of several contractile proteins and certain soluble enzymes. In particular, proliferative smooth muscle contains at least three PDPKs p34 i 2 p42 , and p44 PK the contractile phenotype of smooth muscle, only p42 P and p44 mark have been identified. The precise function and a complete description of the substrates for MAPK in the contractile phenotype of smooth muscle are unknown however, one substrate that has been idenhfied is the actin and myosin binding protein, caldesmon. Because of the phosphorylation of cal-desmon, MAPK may be involved in either smooth muscle contractile regulation or the structural organization of actin filaments within smooth muscle cells. 

A2 or cPLA2), and proteins for which the function of phosphorylation is incompletely understood (caldesmon). In addition to cell growth and proliferation, the activation of MAPK is linked to physiological functions such as osmosensing in yeast, stretch sensing in cardiac tissue, and a potential role in smooth muscle contractile or cytoskeletal function. A complete description of the substrates phosphorylated by MAPK under physiological conditions in different cell types, and the responses controlled by those modifications, are areas of intense investigation. 

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