Muscle II-a PDF

CONTRACTION THEORIES, PHYSIOLOGICAL PROPERTIES OF MOTOR UNITS -2-  Skeletal Muscle Physiology of Contraction How does all this functional anatomy work? – 1st – synaptic transmission at the neuromuscular junction – 2nd – excitation-contract...

CONTRACTION THEORIES, PHYSIOLOGICAL PROPERTIES OF MOTOR UNITS -2-  Skeletal Muscle Physiology of Contraction How does all this functional anatomy work? – 1st – synaptic transmission at the neuromuscular junction – 2nd – excitation-contraction coupling – 3rd – contraction-relaxation cycle  The transverse (T) tubules are an extensive network of muscle cell membrane (sarcolemma) that invaginates deep into the muscle fiber.  The T tubules are responsible for carrying depolarization from action potentials at the muscle cell surface to the interior of the fiber.  The T tubules make contact with the terminal cisternae of the sarcoplasmic reticulum and contain a voltage-sensitive protein called the dihydropyridine receptor.  Membrane depolarization opens the L-type Ca2+ channel (dihydropyridine receptor;DHP).  Mechanical coupling between DHP receptor and the Ca2+ release channel (ryanodine receptor;RyR) causes the RyR channel to open.  Ca2+ exits the SR via the RyR channel and activates troponin C, leading to muscle conctraction. Ryanodine receptor  SARCOMERE Sarcomere contains contractile units (myofilaments) such as thick and thin filaments 1. Thick filaments; largely composed primarily of a protein called myosin (+protein structures) 2. Thin filaments; contains Actin, Troponin, Tropomyosin (+protein structures) SLIDING FILAMENT THEORY OF CONTRACTION “THE SLIDING FILAMENT THEORY” EXPLAINS HOW A MUSCLE CELL CONTRACTS. DURING CONTRACTION, THE SARCOMERE SHORTENS AND THIN AND THICK FILAMENT OVERLAP TO A GREATER DEGREE.  During the contraction the thick and thin filaments do not change length. Actin filaments slide over the myosin filaments, moving toward the M line in the center of the sarcomere. The A band does not change the length, but both the H zone and I band get shorter as the filaments overlap.  MOLECULAR PARTICIPANTS OF SLIDING THEORY The Sliding Filament Theory of muscle contraction involves the activities of five different molecules; In addition to 5 molecules calcium ions are also involved in the process of muscle contraction.  THICK FILAMENTS OF SARCOMERE Myosin is a protein molecule found in the thick filaments. In the muscle cells myosin molecules are bundled together to form the thick filaments.  MYOSIN MOLECULE WITH HINGED HEAD Myosin has a tail and two heads (called cross bridges). The shape of the each individual myosin molecule is similar to golf spoon with two heads. The head (cross bridge) has the ability to move back and forward. The flexing movement of the head provides the power stroke for muscle contraction. MYOSIN MOLECULE WITH HINGED HEAD AND TAIL head tail The tail of myosin has a hinge which allows vertical movement so that the cross bridge can bind to actin. The combination of two hinge points allows for necessary binding and power stroke of the cross bridges.  ATP AND ACTIN BINDING SITES ON MYOSIN The cross brigde has two important binding sites, one site specifically binds ATP the other one binds to actin (the thin filament)  ENERGIZED CROSS BRIDGE ATP is a molecule with a high chemical energy. The binding of ATP into myosin molecule, transfers energy to myosin cross bridge. When ATP is hydrolyzed into ADP and phosphate, the energy is released and transferred to the myosin head. Low energy state High energy state The events of the crossbridge cycle in skeletal muscle https://www.youtube.com/watch?v=BVcgO4p88AA  THIN FILAMENTS OF SARCOMERE Thin filaments are made of these three protein molecules: 1. Actin 2. Tropomyosin 3. Troponin complex  THIN FILAMENTS OF SARCOMERE Thin filaments are made of these three protein molecules: 1. Actin 2. Tropomyosin 3. Troponin complex Actin is the major component of the thin filament. The actin portion of the thin filament is composed of actin subunits twisted into double helical chain. Each actin subunit has a specific binding site for myosin cross bridge (head).  Actin is a globular protein and, in this globular form, is called G-actin.  In the thin filaments, G-actin is polymerized into two strands that are twisted into an α-helical structure to form filamentous actin, called F-actin.  Actin has myosin-binding sites. When the muscle is at rest, the myosin-binding sites are covered by tropomyosin so that actin and myosin cannot interact.  THIN FILAMENTS OF SARCOMERE Thin filaments are made of these three protein molecules: 1. Actin 2. Tropomyosin 3. Troponin complex The regulatory protein, tropomyosin, is also part of the thin filament. Tropomyosin twists around the actin. In the unstimulated muscle, the position of the tropomyosin, covers the binding site of the actin subunits and prevents myosin cross bridge binding.  THIN FILAMENTS OF SARCOMERE Thin filaments are made of these three protein molecules: 1. Actin 2. Tropomyosin 3. Troponin complex To expose the binding sites open for myosin binding the tropomyosin molecule must be moved aside. This is faciliated by the presence of a 3th molecule, called troponin (troponin complex) Troponin is attached and spaced periodically along the tropomyosin strand. TROPONIN COMPLEX Troponin is a heterotrimer consisting of (1) Troponin T (2) Troponin C (3) Troponin I Troponin T  binds to a single molecule of Tropomyosin Troponin I  binds to Actin and inhibits contraction. Facilitates the inhibition of myosin binding to actin by tropomyosin Troponin C  binds Ca2+ promotes the movement of tropomyosin  SIX STEPS OF SINGLE CROSS BRIDGE CYCLING Step 1: Exposure of binding sites on actin Presence of an action potential in the muscle cell membrane. ↓ Release of calcium ions from the terminal cisternae. ↓ Calcium ions rush into the cytosol and bind to the troponin. ↓ Conformational change in the troponin-tropomyosin complex. ↓ Tropomyosin moves away from the myosin binding sites on actin.  Conformational change ↓ Tropomyosin strand moved away Calcium ions Actin binding site Step 2: Binding of myosin to actin When a binding site of actin exposed, energized cross bridge can bind to actin. Step 3: Power stroke of the cross bridge The ADP and Pi are released from the myosin. ↓ The myosin head (cross bridge) tilts backward. ↓ The power stroke occurs as the thin filament is pulled toward the center of the sarcomere. Step 4: Disconnecting the cross bridge In order to disconnect the cross bridge from actin, an ATP molecule must bind to site on the myosin cross bridge. Step 5 : Re-energizing and re-positioning of the cross bridge The release of myosin cross bridge triggers the hydrolysis of ATP into ADP and Pi. Energy is transferred from ATP to myosin cross brigde which returns its high energy state. Step 6: Removal of calcium ions Calcium ions fall off the troponin. ↓ Calcium is activelly transported from cytosol into the sarcoplasmic reticulum by ion pumps. ↓ Tropomyosin again covers the binding sites on actin. The Cross-bridge Cycle Rigor Mortis “Stiffness of death” What is Rigor Mortis? Rigor Mortis is the stiffening of the body after death because of a loss of AdenosineTriphosphate (ATP) from the body's muscles. Rigor Mortis begins throughout the body at the same time but the body's smaller muscles - such as those in the face, neck, arms and shoulders - are affected first and then the subsequent muscles throughout the rest of the body; those which are larger in size, are affected later. In living muscle, the rigor state occurs for only a very brief period.  Relaxation occurs when Ca2+ is reaccumulated in the sarcoplasmic reticulum by the Ca2+ATPase of the sarcoplasmic reticulum membrane (SERCA).  When there is insufficient Ca2+ for binding to troponin C, tropomyosin returns to its resting position, where it blocks the myosin-binding site on actin.  As long as the intracellular Ca2+ is low, cross-bridge cycling cannot occur, and the muscle will be relaxed. Calcium Pumps (SERCA) In a relaxed muscle cell, the concentration of calcium ions are about 10,000 lower in the cytosol than in the SR. During a muscle contraction, the concentration of calcium in the cytosol increases, but it is still higher inside the SR. To move the calcium against the gradient, from the lower concentration in the cytosol to the higher concentration inside the SR, active transport is needed.  Within the sarcoplasmic reticulum, Ca2+ is bound to calsequestrin, a low-affinity, high-capacity Ca2+-binding protein.  Calsequestrin, by binding Ca2+, helps to maintain a low free Ca2+ concentration inside the sarcoplasmic reticulum.  Thus, a large quantity of Ca2+ can be stored inside the sarcoplasmic reticulum in bound form, while the intrasarcoplasmic reticulum free Ca2+ concentration remains extremely low.  REVIEW OF THE ROLE OF ATP ATP plays a key role in the contraction of muscle. 1. Energizing the powerstroke of the myosin cross bridge, 2. Disconnecting the myosin cross bridge from the binding site on actin at the conclusion of a power stroke, 3. Actively transporting calcium ions into the sarcoplasmic reticulum. Thank you