Calcium-troponin complex

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. 

In striated muscle, there are two other proteins that are minor in terms of their mass but important in terms of their function. Tropomyosin is a fibrous molecule that consists of two chains, alpha and beta, that attach to F-actin in the groove between its filaments (Figure 49-3). Tropomyosin is present in all muscular and muscle-fike structures. The troponin complex is unique to striated muscle and consists of three polypeptides. Troponin T (TpT) binds to tropomyosin as well as to the other two troponin components. Troponin I (Tpl) inhibits the F-actin-myosin interaction and also binds to the other components of troponin. Troponin C (TpC) is a calcium-binding polypeptide that is structurally and functionally analogous to calmodulin, an important calcium-binding protein widely distributed in nature. Four molecules of calcium ion are bound per molecule of troponin C or calmodulin, and both molecules have a molecular mass of 17 kDa. 

The contractile proteins of the myofibril include three troponin regulatory proteins. The troponin complex includes three protein subunits, troponin C (the calcium-binding component), troponin I (the inhibitory component), and troponin T (the tropomyosin-binding component). The subunits exist in a number of isoforms. The distribution of these isoforms varies between cardiac muscle and slow- and fast-twitch skeletal muscle. Only two major isoforms of troponin C are found in human heart and skeletal muscle. These are characteristic of slow- and fast-twitch skeletal muscle. The heart isoform is identical with the slow-twitch skeletal muscle isoform. Isoforms of cardiac-specific troponin T (cTnT) and cTnl also have been identified and are the products of unique genes. All cardiac troponins are localized primarily in the myofibrils (94%-97%), with a smaller cytoplasm fraction (3%-6%). 

Cardiac troponin complex consists of three parts. Troponin T facilitates contraction, troponin I (cTnl) inhibits actin-myosin interactions and troponin C binds to calcium ions. Troponin I and T are specific to the heart. In the course of cell damage, cardiac troponin is released Irom myocytes, facilitated by increased membrane permeability that allows smaller troponin fragments to traverse the membrane. 

After death, the ratio of ADP to ATP increases rapidly. In the ADP form, myosin motor domains bind tightly to actin. Myosin-actin interactions are possible because the drop in ATP concentration also allows the calcium concentration to rise, clearing the blockage of actin by tropomyosin through the action of the troponin complex. 

Tropomyosin and the troponin complex regulate this sliding in response to nerve impulses. Under resting conditions, tropomyosin blocks the intimate interaction between myosin and actin. A nerve impulse leads to an in crease in calcium ion concentration within the muscle cell. A component ol the troponin complex senses the increase in Ca" and, in response, relieves the inhibition of myosin—actin interactions by tropomyosin. 

ATP concentration also allows the calcium concentration to rise, clearing the blockage of actin by tropomyosin through the action of the troponin complex. 

Schematic diagram of the organization of skeletal muscle thin filament, showing the position of tropo-myosin and the troponin complex on the actin filament. The binding of Ca " to TnC, the calcium-binding subunit of the troponin complex, removes Tnl, the inhibitory subunit, from actin and thus permits an interaction with a specialized protein, myosin, on neighboring thick muscle filaments (not shown). An ATP-driven conformation change in the myosin head group makes the thick and thin filaments move relative to one another, so that muscle contraction occurs.

Bou-Assaf GM, Chamoun JE, Emmett MR, Fajer PG, Marshall AG. Complexation and calcium-induced conformational changes in the cardiac troponin complex monitored by hydrogen/deuterium exchange and FT-ICR mass spectrometry. Int J Mass Spectrom. 

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... 

Tropomyosin is a fibrous molecule which twists around the F-actin strands. The troponin (Tn) complex is composed of three proteins Tnl (I = inhibitory) which prevents myosin binding to actin in the resting muscle, TnT which binds tropomyosin and TnC (C for calcium-binding). Cardiac muscle troponins are different from those of skeletal muscle and are designated cTnl, cTnT and cTnC. 

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. 

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