Smooth muscle active tension

In smooth muscle, myosin crossbridges have less myosin ATPase activity than those of skeletal muscle. As a result, the splitting of ATP that provides energy to "prime" the crossbridges, preparing them to interact with actin, is markedly reduced. Consequently, the rates of crossbridge cycling and tension development are slower. Furthermore, a slower rate of calcium removal causes the muscle to relax more slowly. 

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... 

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. 

Smooth muscles not only alter their tension in response to changes in the frequency of action potential discharge, but also in response to activation of various receptors... 

Most work on the SR and diseased smooth muscle has concerned vascular smooth muscle in hypertensive animals, and bladders from animal models of outflow obstruction. The tools used to study SR function are mainly indirect, and include recording tension or intracellular [Ca2+] with fluorescent probes, measuring Ca2+ fluxes with 45Ca, and investigating the effects of drugs known to block SERCA or activate store release. More directly, some measurement of the activity of SERCA in microsomal preparations has been undertaken (e.g. Zderic et al 1996). 

S ATP + myosin hght chain <1-12> (<1, 2, 8> event in initiation of smooth-muscle contraction [5] <8> involved in regulation of actin-myosin contractile activity in adrenal medulla [7] <8> obhgatory step in development of active tension in smooth muscle [13] <5> involved in myosin phosphorylation and enzyme secretion [16] <2, 3, 5, 6, 8, 10, 11> involved in muscle contractility and motility of non-muscle cells [33] <2> inhibition of actin-myosin ineraction [36,37]) (Reversibihty 1-12 [1-33]) [1-33]... 

Isolated chondrocytes grown in type I and type II collagen-glycosaminoglycan matrices contract the matrix and immunochemically stain for alpha-smooth muscle actin. These results suggest that chondrocytes can also generate active tension and may be responsible for maintaining the tension in articular cartilage. 

Active stresses exerted by smooth muscle cells appear to increase the internal stresses that exist in vessel wall. The effects of passive and active muscular contraction on the residual stress in the wall have been considered. Their results suggest that basal muscle tone, which exists under physiological conditions, reduces the strain gradient in the arterial wall and yields a near uniform stress distribution. Increased muscular tone that accompanies elevated blood pressure tends to restore the distribution of circumferential strain in the arterial wall, and to maintain the flow-induced wall shear stress at normal levels. It appears that the active stresses exerted by smooth muscle cells may balance the tension within the vessel wall in a similar manner to the way that active fibroblast tension balances the stress in the dermis. 

Protein kinase C (PKC) may play a role in tonic tension. PKC refers to a family of related serine/threonine kinases, five of which are found in smooth muscle. PKC is activated by diacylglycerol, or DAG. DAG (and also IP3) is liberated from membranes by the action of phospholipase C (PLC) on phosphatidylinositol 4,5-bisphosphate, or by the action of phospholipase D (PLD) on phosphatidylcholine. A number of receptor-mediated events are transduced by activation of these lipases. Some agents that elicit tonic contraction (e.g., angiotensin II) activate PLD, thus producing DAG (but not IP3), which activates PKC with no effect on [Ca +]j. There are at least three sites on LC20 that can be phosphorylated by PKC, but it is not known which one, if any, of these is involved in the induction of contraction and latch. 

Control of intracellular Ca, [Ca, in uterine and other smooth muscles is essential for control of tension production. Studies of smooth muscles with plasma membranes damaged by glycerol (JL) or non-ionic detergents (2 .3j.4) or of isolated contractile protein rom sigoth muscle C5,6 1) all suggest that with lejss thgn 10 M Ca. no active tension is produced while at 10 M Ca or perhaps less, maximum active tension is produced. 

Prostaglandin H synthase is the first enzyme involved in the arachidonic acid cascade . The prostaglandins can cause both relaxation and tension in smooth muscle and so have vital physiological roles. Prostaglandin H synthase acts as both a peroxidase and an oxygenase its so-called cyclooxygenase activity involves addition of two equivalents of oxygen to a free radical derived from arachidonic acid to form an endoperoxide... 

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.

Constraints imposed by caldesmon that disrupt potentiation may not block myosin docking on actin. This process of modulating ATPase could in turn lead to or permit the development of the latch-state of tension maintenance displayed by tonic smooth muscles and observed at low Ca + concentration. This phenomenon probably involves stable actin-myosin binding and is associated with low actomyosin ATPase activity (Hai and Murphy, 1988 McDaniel et al, 1990). As envisioned, such tension maintenance would be incompatible with a troponin-tropomyosin form of regulation since tropomyosin would in that case block myosin docking at low Ca + concentrations. Hence, the caldesmon-tropomyosin system may be adapted for muscles that enter a latch-state. 

In triton skinned and in a-toxin-permeabilized smooth muscle preparations, the Ca + sensitivity of force production is also decreased by cGMP (Pfitzer et al., 1984,1986 Nishimura efflZ., 1992). This may be due to an up-regulation of MLCP (Pfitzer etal., 1986). Clear evidence that modulation of the activity of MLCP would affect Ca + sensitivity of tension development was in fact obtained in triton skinned smooth muscle when it was shown that inhibition of MLCP by the black sponge toxin, okadaic acid, increased Ca + sensitivity (Takai et al., 1987 Bialojan et al., 1988). On the other hand, incubation of triton skinned chicken gizzard fibers with a purified phosphatase decreased Ca + sensitivity (Bialojan et al., 1987). 

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