This is an excerpt from Advanced Cardiovascular Exercise Physiology-2nd Edition by Denise L. Smith & Bo Fernhall.
Like all muscle fibers, cardiac muscle fibers (myocytes) contract in response to an electrical signal (action potential) in the cell membrane. Specific features of the cell membrane, along with specialized organelles, are responsible for transmitting the electrical signal into the interior of the cell. The structure of cardiac myocytes has many similarities with that of skeletal muscle (including many organelles and specifically the protein filaments actin and myosin). There are some important differences, however, between skeletal and cardiac muscle; cardiac muscle fibers are shorter and more branched than skeletal muscle fibers. The structure of the myocyte directly supports its function—contracting as part of a functional unit to eject blood from the chambers of the heart.
Myocytes are approximately 50 to 100 mm long and 10 to 20 mm in diameter and have a striated appearance when viewed under a microscope (figure 3.1), which results from the overlapping contractile filaments (thick and thin filaments). The cell membranes of adjacent cardiac muscle cells are attached to one another end to end by a specialized junction: the intercalated disc. Myocytes have a large centrally located nucleus and a large number of mitochondria. Other specialized organelles of the myocyte include transverse tubules (T-tubules) that carry an action potential into the interior of the cell, and sarcoplasmic reticulum that stores and releases calcium.
As with all muscle cells, the sarcolemma of the myocyte is composed of a phospholipid bilayer. As described fully in the following chapter, an action potential is generated when there is a reversal of charge across the cell membrane. The action potential initiates muscle contraction via the sliding of myofilaments over one another. Excitation–contraction coupling links the action potential (excitation) in the cell membrane to force generation (contraction) in the contractile tissue of the myocytes. An action potential in a contractile myocyte is also spread to adjacent myocytes via intercalated discs. The spreading of action potentials to adjacent myocytes ensures that all the myocytes contract at the appropriate time, allowing for the heart to function as an effective pump.
Intercalated discs structurally and functionally connect adjacent myocytes. An intercalated disc is an undulating double membrane separating adjacent cells that contains two primary types of junctions: gap junctions and desmosomes (figure 3.2). The gap junctions are made up of connexons, hexagonal structures that form a connection between two adjacent cells and provide a low-resistance pathway that allows the transmission of ion currents and thus electrical impulses from one myocyte to the next. Because the electrical signal (action potential) can flow from one myocyte to the next, the myocardium behaves as a functional unit—it acts as a syncytium, thus ensuring the effective pumping action of the heart. Desmosomes serve to bind adjacent myocytes together. There is a thickening (called a plaque) on the sarcoplasmic side of both adjacent myocytes at the site of the desmosome. The adjacent myocytes are held together by thin protein filaments (called cadherins) that extend from the plaque and interdigitate like the teeth of a zipper to hold the myocytes together. Thicker filaments (called intermediate filaments) extend from the plaque across the cell to provide additional mechanical and tensile strength to the cell. Because adjacent cells are held together by desmosomes, the myocytes are not pulled apart by the force of contraction.
Myocytes contain long, cylindrical-shaped organelles called myofibrils that are themselves composed of overlapping thick and thin myofilaments (figure 3.3). It is the sliding of these filaments past one another that produces force during muscular contraction. The arrangement of the sarcomeres along the myofibrils, and across the many myofibrils of the muscle cell, gives the muscle cell its striated appearance. The myofibrils of cardiac muscle are very similar in structure, function, and appearance to those of skeletal muscle.
Each myofibril is composed of smaller functional units called sarcomeres that are oriented end to end along the myofibril. The sarcomere is the basic contractile unit of the myocyte. Sarcomeres are composed primarily of overlapping thick and thin filaments, although they also contain additional proteins and connective tissue that constitute the cytoskeleton of the sarcomere and contribute to the mechanical stiffness and elasticity of muscle tissue. A sarcomere extends from one Z disc to the adjacent Z disc. The Z disc that forms the partition of the sarcomere is composed of a-actinin protein. Between the Z discs are the thick and thin filaments. The thick filaments are composed of the contractile protein myosin; the thin filaments are composed primarily of the contractile protein actin. The thin filament also contains the regulatory proteins, troponin and tropomyosin, which play a regulatory role in muscle contraction.
Transverse tubules (T-tubules) are deep invaginations in the sarcolemma at each Z disc that provide the mechanism for transmitting an electrical impulse from the sarcolemma into the myocyte. Because of their number and their ability to spread the electrical signal into the cell rapidly, the T-tubules play an important role in ensuring that all the myofibrils are activated almost simultaneously. The T-tubules are structurally and functionally connected to the sarcoplasmic reticulum, and together these organelles control intracellular calcium levels (figure 3.4).
The sarcoplasmic reticulum (SR) is an extensive series of tubular structures within the myocyte that store and release calcium. The SR accounts for approximately 5% of cell volume and plays a central role in regulating intracellular calcium levels. Intracellular calcium concentrations play a critical role in controlling cardiac muscle contraction. High levels of intracellular calcium concentrations initiate cardiac muscle contraction via binding with regulatory proteins (troponin) on actin. In contrast, myocardial relaxation is achieved primarily by the removal of calcium ions. Thus, it is important to understand how the muscle cell handles calcium, and to realize that myocytes differ from skeletal muscle in the way in which calcium is handled. The SR surrounds the myocyte and comes in close proximity to the Ttubules (figure 3.4). The SR has three distinct regions, each with a specific role in calcium handling. The junctional SR, which contains large stores of calcium, comes very close (within 15 nm) to the sarcolemma and the T-tubules. The area where the junctional SR and T-tubules nearly meet is termed a diad. Protein channels also extend from the junctional SR; these are alternately called calcium release channels, calcium-induced calcium release channels, or ryanodine receptors. They derive these names because they release calcium, because they release calcium when stimulated with calcium, and because they bind the drug ryanodine. In addition to releasing calcium, these receptors also bind to calcium that enters the cell through the sarcolemma or T-tubules (thus they are also sometimes called calcium-induced calcium release channels), making their placement next to the sarcolemma perfectly logical.
Corbular SR is a sac-like expansion of the SR that lies next to the I-bands and contains a high concentration of calcium. Network SR runs in parallel with the T-tubules and is primarily responsible for the uptake of calcium from the sarcoplasm after a muscle contraction. Network SR contains an abundant number of SR calcium-ATPase pumps (SERCA2) to ensure that it can effectively pump calcium into the SR against its concentration gradient. In humans, approximately 75% of calcium ions are removed from the sarcoplasm during relaxation by the SR calcium-ATPase pumps (Hasenfuss, 1998). These calcium-ATPase pumps are regulated by the protein phospholamban.
The normal cycle of systole and diastole requires a precise, transient increase and decrease in the intracellular concentration of calcium ions. The SR plays an integral role in orchestrating the movement of calcium ions with each contraction and relaxation of the heart.
Marist is a collegiate soccer player. He has been playing soccer since was six years old and trains year-round to ensure he is in great shape for the game he loves. During a home game in his senior year, he collapsed on the field. Fortunately, an AED was available on the field and Marist was successfully revived. A cardiac work-up revealed that he had arrhythmogenic right ventricular cardiomyopathy.
- Was this a life-threatening event?
- What cardiac structures are often associated with cardiomyopathies?
- Does this have implications for Marist’s soccer career?