Calcium binding proteins muscle contraction

Sorcin (soluble resistance-related calcium binding protein) was isolated from multidrug-resistant cells and is expressed in a few mammalian tissues such as skeletal muscle, heart, and brain. In the heart, sorcin interacts with the ryanodine receptor and L-type Ca2+-channels regulating excitation in contraction coupling. 

The calcium mediated contraction of smooth muscle, which unlike striated muscle does not contain troponin, is quite different and requires a particular calcium-binding protein called calmodulin. Calmodulin (CM) is a widely distributed regulatory protein able to bind, with high affinity, four Ca2+ per protein molecule. The calcium—calmodulin (CaCM) complex associates with, and activates, regulatory proteins, usually enzymes, in many different cell types in smooth muscle the target regulatory proteins are caldesmon (CDM) and the enzyme myosin light chain kinase (MLCK). As described below, CaCM impacts on both actin and myosin filaments. 

Intracellular ionized calcium acts as a second messenger, coupling the action of a hormone or electrical impulse (the first messenger) on the outside of the cell to intracellular events, such as hormone or protein secretion, protein kinase activity, or muscle contraction. The effect of Ca on intracellular processes is often mediated by a small calcium-binding protein, such as troponin C in muscle (Chapter 21) or calmodulin in many other cells (Chapters 15 and 30). Synthesis of these calciumbinding proteins is not directly affected by vitamin D or any of its metabolites. Many stimuli that affect permeability to calcium also activate membrane-bound adenylate cyclase and increase the intracellular concentration of cAMP (Chapter 30). 

Caldesmon is a cytoplasmic protein with two isoform classes, one of which is found predominantly in smooth muscle cells and other cell types with partial myogenic differentiation. High-molecular-weight isoforms with molecular weights between 89 and 93 kD are capable of binding to actin, tropomyosin, calmodulin, myosin, and phospholipids, and they function to counteract actin-tropomyosin-activated myosin adenosine triphosphatase (ATPase). As such, they are mediators for the inhibition of calcium-dependent smooth muscle contraction." ... 

Troponin is the regulatory complex of three proteins of the thin filament of myocytes. Troponin T binds to tropomyosin, troponin I is an inhibitory protein, and troponin C binds to calcium needed for muscle contraction. Following irreversible myocyte damage, unbound troponin subunits are initially released into blood from the cytosolic pools. This is followed by a sustained release of the tri-troponin complex due to the breakdown of the myocyte itself. Once in blood, the complex is further degraded into the binary troponin I-C complex, and frees troponin T. Figure 92.1 shows the kinetics of troponin subunit release. Troponin is superior to the other biomarkers for cardiac injury for two... 

Calcium is the trigger behind the muscle contraction process (24,25). Neural stimulation activates the release of stored Ca(Il) resulting in a dramatic increase in free calcium ion levels. The subsequent binding of Ca(Il) resulting in a dramatic increase in free calcium ion levels. The subsequent binding of Ca(Il) to the muscle protein troponin C provides the impetus for a conformational change in the troponin complex and sets off successive events resulting in muscle contraction. 

Another mechanism in initiating the contraction is agonist-induced contraction. It results from the hydrolysis of membrane phosphatidylinositol and the formation of inositol triphosphate (IP3)- IP3 in turn triggers the release of intracellular calcium from the sarcoplasmic reticulum and the influx of more extracellular calcium. The third mechanism in triggering the smooth muscle contraction is the increase of calcium influx through the receptor-operated channels. The increased cytosolic calcium enhances the binding to the protein, calmodulin [73298-54-1]. 

More than 99% of total body calcium is found in bone the remaining less than 1% is in the ECF and ICE Calcium plays a critical role in the transmission of nerve impulses, skeletal muscle contraction, myocardial contractions, maintenance of normal cellular permeability, and the formation of bones and teeth. There is a reciprocal relationship between the serum calcium concentration (normally 8.6 to 10.2 mg/dL [2.15 to 2.55 mmol/L]) and the serum phosphate concentration that is regulated by a complex interaction between parathyroid hormone, vitamin D, and calcitonin. About one-half of the serum calcium is bound to plasma proteins the other half is free ionized calcium. Given that the serum calcium has significant protein binding, the serum calcium concentration must be corrected in patients who have low albumin concentrations (the major serum protein). The most commonly used formula adds 0.8 mg/dL (0.2 mmol/L) of calcium for each gram of albumin deficiency as follows ... 

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

These drugs act by binding to Pj-adrenoceptors on myometrial cell membranes and activating adenylyl cyclase. This in turn increases levels of cAMP in the cell (Fig. 62.1), activating cAMP-dependent protein kinase, hence decreasing intracellular calcium concentrations and reducing the effect of calcium on muscle contraction. 

Regulatory processes such as muscle contraction are controlled by temporary conformational changes associated with metal ion co-ordination. Such regulatory processes are frequently associated with metal ions such as Mg2+, Ca2+ and Mn2+ (which possesses a d5 configuration with no crystal field preference for any particular co-ordination geometry). Muscle contraction is controlled by the binding of calcium ions to the protein troponin (Fig. 10-4), with a feed-back loop controlling the release and uptake of calcium ions from an ATP-ase, an enzyme which catalyses the hydrolysis of ATR... 

Ion binding is essential for a variety of physiological processes. The binding of calcium ions by some protein triggers the process to induce the muscle contraction and enzymatic reactions [40,41], The initial process of the information... 

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