Excitation contraction coupling refers to the sequence of events by which an action potential in the plasma membrane activates the force generating mechanisms. An action potential in a skeletal muscle fiber lasts 1 to 2 msec and is completed before any signs of mechanical activity begins. The electrical activity in the plasma membrane produces a state of increased cytosolic Ca2+ concentration, which continues to activate the contractile apparatus long after the electrical activity in the membrane has ceased. Tropomyosin is a rod-shaped molecule composed of 2 intertwined polypeptides. Chains of tropomyosin molecules are arranged end to end along the actin thin filament. These tropomyosin molecules partially cover the myosin binding site on each action monomer, thereby, preventing the cross bridges from making contact with actin. Each tropomyosin molecule is held in this blocking position by the small globular protein, troponin. Troponin, which interacts with both actin and tropomyosin, is composed of 3 subunits designated by letter I (inhibitory), T (tropomyosin binding) and C (Ca2+ binding). One molecule of troponin binds to each molecule of tropomyosin and regulates the access to myosin-binding sites on the T action monomers in contact with that tropomyosin. This is the status of a resting muscle fiber; troponin and tropomyosin cooperatively block the interaction of cross-bridges with the thin filament.
When Ca2+ binds to specific binding sites on Ca2+ binding subunits of troponin. The binding of Ca2+ produces a change in the shape of troponin, which releases its inhibitory grip and allow tropomyosin to move away from the myosin binding site on each actin molecule. Conversely, the removal of Ca2+ from troponin reverses the process, turning off the contractile activity. In a resting muscle fiber, the concentration of free, ionized calcium in the cytosol surrounding the thick and thin filaments is very low only about 10^27 mole/L. At this low Ca2+ concentration, very few of the Ca2+ binding sites on troponin are occupied and others cross bridges activity is blocked by tropomyosin. Following an action potential, there is a rapid increase in cytosolic Ca2+ concentration and Ca2+ binds to troponin removing the blocking effect of tropomyosin and allowing myosin cross-bridges to bind actin.
A specialized mechanism couples T-tubule action potentials with Ca2+ release from Sarcoplasmic reticulum. The T-tubule protein is a modified voltage sensitive Ca2+ channel known as dihydropyridine receptor (DHP). The main role of DHP receptor, however, is not to conduct Ca2+ but rather to act as a voltage sensor. The protein embedded in sarcoplasmic reticulum membrane is known as ryanodine receptor. This large molecule not only includes foot processes but also form a Ca2+ channel. During a T-tubule action potential, charged amino acid residues within a DHF receptor protein induce a conformational change, which acts via the foot process to open the ryanodine receptor channel. Ca2+ is thus released from terminal cisternae of sarcoplasmic reticulum into cytosol, where it can bind to troponin. The increase in cytosolic Ca2+ in response to a single action potential is enough to briefly saturate all troponin binding sites on actin.
A contraction is terminated by removal of Ca2+ from troponin. The membranes of sarcoplasmic reticulum contain primary active transport proteins Ca2+ ATPase- that pump calcium ions from cytosol back into the lumen of reticulum.
When Ca2+ binds to specific binding sites on Ca2+ binding subunits of troponin. The binding of Ca2+ produces a change in the shape of troponin, which releases its inhibitory grip and allow tropomyosin to move away from the myosin binding site on each actin molecule. Conversely, the removal of Ca2+ from troponin reverses the process, turning off the contractile activity. In a resting muscle fiber, the concentration of free, ionized calcium in the cytosol surrounding the thick and thin filaments is very low only about 10^27 mole/L. At this low Ca2+ concentration, very few of the Ca2+ binding sites on troponin are occupied and others cross bridges activity is blocked by tropomyosin. Following an action potential, there is a rapid increase in cytosolic Ca2+ concentration and Ca2+ binds to troponin removing the blocking effect of tropomyosin and allowing myosin cross-bridges to bind actin.
A specialized mechanism couples T-tubule action potentials with Ca2+ release from Sarcoplasmic reticulum. The T-tubule protein is a modified voltage sensitive Ca2+ channel known as dihydropyridine receptor (DHP). The main role of DHP receptor, however, is not to conduct Ca2+ but rather to act as a voltage sensor. The protein embedded in sarcoplasmic reticulum membrane is known as ryanodine receptor. This large molecule not only includes foot processes but also form a Ca2+ channel. During a T-tubule action potential, charged amino acid residues within a DHF receptor protein induce a conformational change, which acts via the foot process to open the ryanodine receptor channel. Ca2+ is thus released from terminal cisternae of sarcoplasmic reticulum into cytosol, where it can bind to troponin. The increase in cytosolic Ca2+ in response to a single action potential is enough to briefly saturate all troponin binding sites on actin.
A contraction is terminated by removal of Ca2+ from troponin. The membranes of sarcoplasmic reticulum contain primary active transport proteins Ca2+ ATPase- that pump calcium ions from cytosol back into the lumen of reticulum.
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