receptors represent the majority of intracellular Ca²+ channels in cardiomyocytes and arbitrate a process known as Ca²+ induced Ca²+ release. The free Ca²+ binds to the troponin C present on the actin-containing thin filaments of myofibrils. Troponin proteins consists of three different subunits, Troponin T, Troponin I, and Troponin C, with each subunit being responsible for a different part of troponin function. Troponin T is a tropomyosin-binding subunit and hence regulates the interaction of the troponin complex with actin thin filaments, troponin I is an inhibitor of the ATP-ase activity of myosin and responsible for the inability of myosin binding to actin in the relaxed muscle. Finally, troponin C is the Ca²+ binding subunit and plays
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Upon Ca²+ binding to the troponin C subunit, the troponin complex undergoes an allosteric conformation change which allows tropomyosin to move, unblocking the binding sites for myosin which tightly binds to the newly uncovered binding sites on the thin filament. Using ATP-hydrolysis the myosin head pulls the Z-lines of the actin filament towards each other leading to a shortening of the sarcomeres and the I-band, and the cardiomyocyte contracts (6) (7) (8). Several mechanisms allow a removal of Ca²+ from the cytosol for muscle relaxation including active Ca²+ uptake into the sarcoplasmatic reticulum via the sarco-endoplasmic reticulum Ca²+ transporter (SERCA) (9) and ejection through the sarcolemma by virtue of the Na+/Ca2+ exchanger (10) as major mechanisms. The net result of these changes is recurrent increases and decreases in Ca²+ concentration and individual cardiomyocyte contractility (Figure …show more content…
The socioeconomic burden of cardiovascular disease is forecasted to exceed $1 trillion per year in the United States alone by 2030 (12). Similar statistics are true for Europe, each year the disease causes over 4 million deaths in Europe and over 1.9 million deaths in the European Union. This makes it the major cause of death for both men and women in most countries of Europe (13). Heart failure and myocardial infarction result in cardiomyocyte death by apoptosis and/or necrosis. The cardiomyocytes’ limited capability to divide leads to the replacement of dead cells by proliferating fibroblast that migrate into the damaged area to form scar tissue (fibrosis). The fibrotic scar tissue results in the development of a thin ventricular wall, which no longer possesses proper contraction ability and initiates a series of events that trigger remodeling, hypertrophy, and ultimately heart failure and further cell death (16). Stem and progenitor cells possess the potential to generate cardiomyocytes in the human heart, but it has been difficult to establish whether cardiomyocytes can be generated or duplicated after the perinatal period. Insufficient regeneration and loss of cardiomyocytes often results in chronic heart failure, and this has prompted for cardiomyocyte replacement therapies using stem cell-based approaches to maintain
Upon Ca²+ binding to the troponin C subunit, the troponin complex undergoes an allosteric conformation change which allows tropomyosin to move, unblocking the binding sites for myosin which tightly binds to the newly uncovered binding sites on the thin filament. Using ATP-hydrolysis the myosin head pulls the Z-lines of the actin filament towards each other leading to a shortening of the sarcomeres and the I-band, and the cardiomyocyte contracts (6) (7) (8). Several mechanisms allow a removal of Ca²+ from the cytosol for muscle relaxation including active Ca²+ uptake into the sarcoplasmatic reticulum via the sarco-endoplasmic reticulum Ca²+ transporter (SERCA) (9) and ejection through the sarcolemma by virtue of the Na+/Ca2+ exchanger (10) as major mechanisms. The net result of these changes is recurrent increases and decreases in Ca²+ concentration and individual cardiomyocyte contractility (Figure …show more content…
The socioeconomic burden of cardiovascular disease is forecasted to exceed $1 trillion per year in the United States alone by 2030 (12). Similar statistics are true for Europe, each year the disease causes over 4 million deaths in Europe and over 1.9 million deaths in the European Union. This makes it the major cause of death for both men and women in most countries of Europe (13). Heart failure and myocardial infarction result in cardiomyocyte death by apoptosis and/or necrosis. The cardiomyocytes’ limited capability to divide leads to the replacement of dead cells by proliferating fibroblast that migrate into the damaged area to form scar tissue (fibrosis). The fibrotic scar tissue results in the development of a thin ventricular wall, which no longer possesses proper contraction ability and initiates a series of events that trigger remodeling, hypertrophy, and ultimately heart failure and further cell death (16). Stem and progenitor cells possess the potential to generate cardiomyocytes in the human heart, but it has been difficult to establish whether cardiomyocytes can be generated or duplicated after the perinatal period. Insufficient regeneration and loss of cardiomyocytes often results in chronic heart failure, and this has prompted for cardiomyocyte replacement therapies using stem cell-based approaches to maintain