Cardiovascular Physiology Week 2 PDF

Week 2: Cardiovascular Physiology Cardiac Muscle Contraction Myocardial cell structure There are several morphologic and functional differences between cardiac muscle and skeletal muscle, but the basic contractile machinery in the two cell types is similar. As in skeletal muscle, the cardiac musc...

Week 2: Cardiovascular Physiology Cardiac Muscle Contraction Myocardial cell structure There are several morphologic and functional differences between cardiac muscle and skeletal muscle, but the basic contractile machinery in the two cell types is similar. As in skeletal muscle, the cardiac muscle cell is composed of sarcomeres. The sarcomeres, which run from Z line to Z line, are composed of thick and thin filaments. The thick filaments are composed of myosin, whose globular heads have actin-binding sites and ATPase activity. The thin filaments are composed of three proteins: actin, tropomyosin, and troponin. o Actin is a globular protein with a myosin-binding site, which, when polymerized, forms two twisted strands. o Tropomyosin runs along the groove of the twisted actin strands and functions to block the myosin-binding site. o Troponin is a globular protein composed of a complex of three subunits; the troponin C subunit binds Ca²⁺. When Ca²⁺ is bound to troponin C, a conformational change occurs, which removes the tropomyosin inhibition of actin-myosin interaction. As in skeletal muscle, contraction occurs according to the sliding filament model, which states that when cross-bridges form between myosin and actin and then break, the thick and thin filaments move past each other. As a result of this cross-bridge cycling, the muscle fiber produces tension. The transverse (T) tubules invaginate cardiac muscle cells at the Z lines, are continuous with the cell membranes, and function to carry action potentials to the cell interior. The T tubules form dyads with the sarcoplasmic reticulum (SR), which is the site of storage and release of Ca²⁺ for excitation-contraction coupling. Excitation-contraction coupling As in skeletal and smooth muscle, excitation-contraction coupling in cardiac muscle translates the action potential into the production of tension. The following steps are involved in excitation-contraction coupling in cardiac muscle: 1. The cardiac action potential is initiated in the myocardial cell membrane, and the depolarization spreads to the interior of the cell via the T tubules. A unique feature of the cardiac action potential is its plateau (phase 2), which results from an increase in gCa and an inward Ca²⁺ current in which Ca²⁺ flows through L-type Ca²⁺ channels (dihydropyridine receptors) from extracellular fluid (ECF) to intracellular fluid (ICF). 2. Entry of Ca²⁺ into the myocardial cell produces an increase in intracellular Ca²⁺ concentration. This increase in Ca²⁺ is not sufficient alone to initiate contraction, but it triggers the release of more Ca²⁺ from stores in the SR through Ca²⁺ release channels (ryanodine receptors). This process is called Ca²⁺-induced Ca²⁺ release, and the Ca²⁺ that enters during the plateau of the action potential is called the trigger Ca²⁺. Two factors determine how much Ca²⁺ is released from the SR: o The amount of Ca²⁺ previously stored, and o The size of the inward Ca²⁺ current during the plateau. Week 2: Cardiovascular Physiology 3. Ca²⁺ release from the SR causes the intracellular Ca²⁺ concentration to increase further. Ca²⁺ now binds to troponin C, tropomyosin is moved out of the way, and the interaction of actin and myosin can occur. o Actin and myosin bind, cross-bridges form and break, and the thin and thick filaments move past each other, producing tension. o Cross-bridge cycling, fueled by ATP, continues as long as the intracellular Ca²⁺ concentration is high enough to occupy the Ca²⁺-binding sites on troponin C. 4. The magnitude of the tension developed by myocardial cells is proportional to the intracellular Ca²⁺ concentration. Hormones, neurotransmitters, and drugs that alter the inward Ca²⁺ current during the action potential plateau or the SR Ca²⁺ stores change the tension produced by myocardial cells. 5. Relaxation occurs when Ca²⁺ is reaccumulated in the SR by the action of the Ca²⁺ ATPase (SERCA). Additionally, Ca²⁺, which entered the cell during the plateau, is extruded by: o Ca²⁺ ATPase, and o Ca²⁺-Na⁺ exchange in the sarcolemmal membrane. These processes reduce intracellular Ca²⁺ concentration to resting levels, causing Ca²⁺ to dissociate from troponin C, blocking actin-myosin interaction, and initiating relaxation. 1. Cardiac action potential ↓ 2. Ca²⁺ enters the cell during the plateau (L-type Ca²⁺ channels) ↓ 3. Ca²⁺-induced Ca²⁺ release from SR (sarcoplasmic reticulum) ↓ 4. Ca²⁺ binds to troponin C ↓ 5. Cross-bridge cycling ↓ Tension Relaxation: Ca²⁺ reaccumulated in SR (via Ca²⁺ ATPase) Cross-bridge cycling stops, leading to muscle relaxation.