108 Cardiac Muscle Tissue

Microscopic Anatomy

Cardiac muscle appears striated due to the presence of sarcomeres, the highly-organized basic functional unit of muscle tissue.

Cardiac muscle, like skeletal muscle, appears striated due to the organization of muscle tissue into sarcomeres. While similar to skeletal muscle, cardiac muscle is different in a few ways. Cardiac muscles are composed of tubular cardiomyocytes, or cardiac muscle cells. The cardiomyocytes are composed of tubular myofibrils, which are repeating sections of sarcomeres. Intercalated disks transmit electrical action potentials between sarcomeres.

Sarcomere Structure

A sarcomere is the basic unit of muscle tissue in both cardiac and skeletal muscle. Sarcomeres appear under the microscope as striations, with alternating dark and light bands. Sarcomeres are connected to a plasma membrane, called a sarcolemma, by T-tubules, which speed up the rate of depolarization within the sarcomere.

Individual sarcomeres are composed of long, fibrous proteins that slide past each other when the muscles contract and relax. The two most important proteins within sarcomeres are myosin, which forms a thick, flexible filament, and actin, which forms the thin, more rigid filament. Myosin has a long, fibrous tail and a globular head which binds to actin. The myosin head also binds to ATP, the source of energy for muscle movement. Actin molecules are bound to the Z-disc, which forms the borders of the sarcomere. Together, myosin and actin form myofibrils, the repeating molecular structure of sarcomeres.

Myofibril activity is required for muscle contraction on the molecular level. When ATP binds to myosin, it separates from the actin of the myofibril, which causes a contraction. Muscle contraction is a complex process regulated by calcium influx and the stimulus of electrical impulses.

Intercalated Discs

Intercalated discs are gap junctions that link cardiomyocytes so that electrical impulses (action potentials) can travel between cells. In a more general sense, an intercalated disk is any junction that links cells together between a gap in which no other cells exist, such as an extracellular matrix. In cardiac muscle tissue, they are also responsible for transmission of action potentials and calcium during muscle contraction. In cardiac muscle, intercalated discs connecting cardiomyocytes to the syncytium, a multinucleated muscle cell, to support the rapid spread of action potentials and the synchronized contraction of the myocardium. Intercalated discs consist of three types of cell-cell junctions, most of which are found in other tissues besides cardiac muscle:

1. Adherens junctions, which anchor actin filaments to cytoplasm of cardiomyocytes.
2. Desmosomes, which bind adhesion proteins to the cytoskeleton within cells, thus connecting the cells.
3. Gap junctions, which connect proteins to the cytoplasm of different cells and transmit action potentials between both cells, required for cellular depolarization. It is found primarily in nervous and muscular tissue.

Under light microscopy, intercalated discs appear as thin lines dividing adjacent cardiac muscle cells and running perpendicular to the direction of muscle fibers.

Mechanism and Contraction Events of Cardiac Muscle Fibers

Cardiac muscle fibers undergo coordinated contraction via calcium-induced calcium release conducted through the intercalated discs.

Cardiomyocytes are capable of coordinated contraction, controlled through the gap junctions of intercalated discs. The gap junctions spread action potentials to support the synchronized contraction of the myocardium. In cardiac, skeletal, and some smooth muscle tissue, contraction occurs through a phenomenon known as excitation contraction coupling (ECC). ECC describes the process of converting an electrical stimulus from the neurons into a mechanical response that facilitates muscle movement. Action potentials are the electrical stimulus that elicits the mechanical response in ECC.

Calcium-Induced Calcium Release

In cardiac muscle, ECC is dependent on a phenomenon called calcium-induced calcium release (CICR), which involves the influx of calcium ions into the cell, triggering further release of ions into the cytoplasm. The mechanism for CIRC is receptors within the cardiomyocyte that bind to calcium ions when calcium ion channels open during depolarization, releasing more calcium ions into the cell.

Similarly to skeletal muscle, the influx of sodium ions causes an initial depolarization; however, in cardiac muscle, the influx of calcium ions sustains the depolarization so that it lasts longer. CICR creates a “plateau phase” in which the cell’s charge stays slightly positive (depolarized) briefly before it becomes more negative as it repolarizes due to potassium ion influx. Skeletal muscle, by contrast, repolarizes immediately.

Pathway of Cardiac Muscle Contraction

The actual mechanical contraction response in cardiac muscle occurs via the sliding filament model of contraction. In the sliding filament model, myosin filaments slide along actin filaments to shorten or lengthen the muscle fiber for contraction and relaxation. The pathway of contraction can be described in five steps:

1. An action potential, induced by the pacemaker cells in the sinoatrial (SA) and atrioventricular (AV) nodes, is conducted to contractile cardiomyocytes through gap junctions.
2. As the action potential travels between sarcomeres, it activates the calcium channels in the T-tubules, resulting in an influx of calcium ions into the cardiomyocyte.
3. Calcium in the cytoplasm then binds to cardiac troponin-C, which moves the troponin complex away from the actin binding site. This removal of the troponin complex frees the actin to be bound by myosin and initiates contraction.
4. The myosin head binds to ATP and pulls the actin filaments toward the center of the sarcomere, contracting the muscle.
5. Intracellular calcium is then removed by the sarcoplasmic reticulum, dropping intracellular calcium concentration, returning the troponin complex to its inhibiting position on the active site of actin, and effectively ending contraction as the actin filaments return to their initial position, relaxing the muscle.

Energy Requirements

Cardiac cells contain numerous mitochondria, which enable continuous aerobic respiration and production of adenosine triphosphate (ATP) for cardiac function.

The heart muscle pumps continuously throughout life and is adapted to be highly resistant to fatigue. Cardiomyocytes contain large numbers of mitochondria, the powerhouse of the cell, enabling continuous aerobic respiration and ATP production required for mechanical muscle contraction. Cardiac muscle tissue has among the highest energy requirements in the human body (along with the brain) and has a high level of mitochondria and a constant, rich, blood supply to support its metabolic activity.

Aerobic Metabolism

Aerobic metabolism is a necessary component to support the metabolic function of the heart. Oxygen is necessary, and if even a small part of the heart is oxygen-deprived for too long, a myocardial infarction (heart attack) will occur. Coronary circulation branches from the aorta soon after it leaves the heart, and supplies the heart with the nutrients and oxygen needed to sustain aerobic metabolism. Cardiac muscle cells contain larger amounts of mitochondria than other cells in the body, enabling higher ATP production.

The heart derives energy from aerobic metabolism via many different types of nutrients. Sixty percent of the energy to power the heart is derived from fat (free fatty acids and triglycerides), 35% from carbohydrates, and 5% from amino acids and ketone bodies from proteins. These proportions vary widely with available dietary nutrients. Malnutrition will not result in the death of heart tissue in the way that oxygen deficiency will, because the body has glucose reserves that sustain the vital organs of the body and the ability to recycle and use lactate aerobically.

Anaerobic Metabolism

While aerobic respiration supports normal heart activity, anaerobic respiration may provide additional energy during brief periods of oxygen deprivation. Lactate, created from lactic acid fermentation, accounts for the anaerobic component of cardiac metabolism. At normal metabolic rates, about 1% of energy is derived from lactate, and about 10% under moderately hypoxic (low oxygen) conditions. Under more severe hypoxic conditions, not enough energy can be liberated by lactate production to sustain ventricular contraction, and heart failure will occur.

Lactate can be recycled by the heart and provides additional support during nutrient deprivation. Recycling lactate is very energy-efficient in the nutrient-deprived myocardium, since one NAD+ is reduced to NADH and H+ (equal to 2.5 or 3 ATP) when lactate is oxidized to pyruvate. The produced pyruvate can then be burned aerobically in the citric acid cycle (also known as the tricarboxylic acid cycle or Krebs cycle), liberating a significant amount of energy.