NMD1104 L12 Histology of the cardiac muscle notes 2024.pdf

L 12 Microstructure of the cardiac muscle ILOs By the end of this lecture, students will be able to 1. 2. 3. 4. Correlate histological features of the cardiac muscle to its function. Identify parts of the intercalated disc & role in myocardium contraction. Identify the sarcomere as the functional un...

L 12 Microstructure of the cardiac muscle ILOs By the end of this lecture, students will be able to 1. 2. 3. 4. Correlate histological features of the cardiac muscle to its function. Identify parts of the intercalated disc & role in myocardium contraction. Identify the sarcomere as the functional unit of the myofibril. Recognize sources of Ca ions. General Features The cardiac muscle is an involuntary muscle that possesses an inherent rhythmicity and contracts spontaneously. Histologically, it is a striated muscle. It forms the middle layer of the heart, the myocardium. Histological features (Fig.1) The cardiac muscle is formed of an anastomosing network of long cylindrical and branching cardiac muscle fibers. They arranged in layers, separated from one another by slender connective tissue sheets. Each muscle fiber is formed of joined cells, the myocytes, which are attached to each other by junctional complexes referred to as intercalated disks. Cardiac muscle fibers stain intensely eosinophilic (WHY?) by the light microscope and myofibrils appear transversely striated, with dark A-bands alternating with light I-bands (Fig 2A). Each myocyte has a single nucleus that is mostly central. Types of myocytes 1. Pacemaker (conduction pathway) myocytes that are characterized by automaticity with limited contractile ability. 2. Contractile myocytes. Components of the intercalated disks and their functional significance a. Intercalated disks have transverse portions (oriented almost perpendicular to muscle fibers), which are formed of fasciae adherentes and desmosomes. Such intercellular junctions provide physical attachment and mechanical stability to prevent separation of myocytes during contraction. b. Lateral portions that are rich in gap junctions. They allow rapid flow of ions between adjacent myocytes, thus establish electrical and metabolic coupling. Figure 1. Cardiac muscle fibers & Intercalated disks 1 Intercalated disks Components of the sarcoplasm of contractile myocytes The predominant components of the sarcoplasm (cytoplasm of the myocyte) are myofibrils that represent groups of myofilaments (protein filaments) arranged parallel to each other. Myofilaments are composed of thick myosin filaments and three types of thin myofilaments; mainly actin, together with tropomyosin and troponin complex. Each myofibril shows transverse striations with alternating A & I-bands. Structural organization of Myofibrils (Fig. 2) Myofibrils are registered parallel to each other with alignment of A-bands of all myofibrils on the same level, as well as, I-bands. Thereby, the myofibrils, as well as, the cardiac muscle fibers appear transversely striated (Fig. 2A). The dark A-bands contain both myosin and thin myofilaments arranged in a parallel and interdigitating pattern, while the I-bands contain only thin myofilaments. In the central zone of each A-band, there is a paler area; the H-zone that contains only myosin filaments that do not overlap with actin. Each I-band is bisected by a dark Z-line that represents an anchoring protein, which fixes the plus end of actin filaments, while the other end of actin ends freely in the center of the A-band at the boundaries of H-zone. The sarcomere (Fig. 2B) The sarcomere is a zone of the myofibril extending between two successive Z-lines. It represents the functional unit of the myofibril in which myosin and actin filaments interact during muscle contraction. Each sarcomere contains two sets of actin filaments, originating from two successive Z-lines of two light I-bands and terminate at the level of the H-zone. Myosin filaments are arranged in a parallel overlapping fashion within the A-bands (the central part of the sarcomere) and are free from both ends. However, they are maintained their arrangement within the A-band by Myomesin-protein that wraps the myosin filaments and forms a dark line, the M-line, in the center of the H-zone. Figure 2. Histological features of cardiac muscle fibers & the sarcomere A B A band 2 Molecular Structure of Myofilaments (Fig 3) A- Thin Filaments Thin filaments are composed of two chains of F-actin filaments wrapped around each other in a helix form, in association with tropomyosin and troponin. I. The major component of each thin filament is filamentous F-actin, a polymer of globular G-actin units. Each G-actin unit has an active site, where the head region of myosin binds (myosin binding site). II. Tropomyosin filaments Pencil-shaped tropomyosin molecules, polymerize to form head-to-tail filaments that occupy the shallow grooves of the double-stranded actin helix. Bound tropomyosin masks the active sites on the G-actin molecules by partially overlapping them, thus do not allow interaction between actin and myosin during muscle relaxation. III. Each troponin molecule, is composed of three globular subunits: TnT, TnC, and TnI. The TnT subunit binds the entire troponin molecule to tropomyosin; TnC has a great affinity for binding calcium ions; and TnI binds to actin, inhibiting the interaction between actin and myosin. B- Myosin Filaments Each myosin filament is composed of about 300 myosin molecules. Each myosin molecule is composed of two parts; a rod-like tail formed of two rod-like polypeptide chains that are wrapped around each other in a helix pattern. The other portion is two globular heads that bind ATP and G-actin forming cross bridges during muscle contraction. Figure 3. The molecular Structure of Myofilaments 3 How are cross bridges formed? Binding of calcium by TnC induces a conformational shift in tropomyosin, exposing the previously blocked active sites on the actin filament so that myosin molecules can form cross-bridges, by binding to the active site on the G-actin molecule. During muscle contraction, thin myofilaments are pulled in (slide) over the myosin filaments resulting in shortening of sarcomeres (Fig. 4). Figure 4. Cross bridges Ultra structure of the cardiac myocyte a. The Transverse (T) tubule It is inward invagination of sarcolemma into sarcoplasm that extends deeply in a transverse direction in relation to myofibrils. It is situated at the level of the Z-line Functions 1. It allows propagation of electrical changes that occur on the sarcolemma into the sarcoplasm, which results in release of stored Ca ions from the sarcoplasmic reticulum. As such, it is responsible for Excitation contraction coupling. 2. It has a wide diameter, thus represents an essential route for Influx of Ca ions from the extra cellular fluid. b. The sarcoplasmic reticulum The sarcoplasmic reticulum (SR) of cardiac muscle is not as extensive as in skeletal muscle; instead, it is represented by small anastomosing tubules and dilated terminals of sarcoplasmic reticulum that approximate the T tubules. The association is usually limited to two partners, resulting in a dyad. The dilated SR terminal is responsible for storage of Ca during muscle relaxation. 4 Sources of intra cellular Calcium ions: 1. 25% of Ca ions enter into the sarcoplasm from the extracellular fluid through the T-tubules that possess voltage gated Ca channels. This stimulates release of stored Ca ions from the SR. 2. 75% of Ca ions is released from the sarcoplasmic reticulum upon depolarization of the sarcolemma and following influx of extra cellular Ca ions. How is relaxation induced? By pumping out of Ca ions across sarcolemma Pumping in Ca ions back into the SR Both steps are ATP dependent. c. Mitochondria Abundant mitochondria are present in the perinuclear sarcoplasm and in between the myofibrils. Figure 5. Ultra structure of the cardiac muscle myocytes 5