Cardiac muscle – Anatomy, Structure, Functions

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.

Cellular

The cellular physiology for the heart is complicated and will be broken down into two sections: the action potential, which is unique in the heart to other action potentials in the body, and electrophysiology.

Action Potential

Please see the image following this article for visual representation

Cardiac Myocyte

The action potential (AP) in the heart is unique to other action potentials in the body. It has five distinct phases numbered 0-4. The resting potential or baseline of the AP is rough – 90 mV and is considered phase 4. For understanding, depolarization is considered the voltage change from the resting potential of – 90 mV toward a positive value. Repolarization will be represented by the return of the voltage of the cell from a positive value down to its resting potential of – 90 mV. The ultimate conclusion of a completed AP is a contraction of the cardiac myocyte.[rx][rx]

There are multiple types of potassium channels involved in the cardiac myocyte AP. To begin, phase 4 is at resting potential and consists of the first set of potassium channels open, with positively-charged potassium flowing out of the cell and thus keeping the voltage low at approximately – 90 mV. This set of potassium channels is passively open and consistently outflows potassium during phase 4.

In the next phase, phase 0, sodium channels open at approximately – 70 mV. The initial depolarization from – 90 mV to – 70 mV is caused by positive sodium and calcium ions entering the cell through gap junctions from neighboring cells. These ions depolarize the voltage just enough to open these voltage-gated (VG) sodium channels which further depolarize the cell to approximately + 50 mV. These voltage-gated sodium channels close very quickly upon depolarizing the cell.

Upon reaching peak voltage, voltage-gated potassium channels open and move potassium out of the cell, decreasing voltage once again. This is known as phase 1.

In phase 2, the plateau phase, potassium channels are open out of the cell, and voltage-gated calcium channels begin to open into the cell. This creates a net balance of charge in the cell, creating a plateau.

With phase 3, the voltage-gated calcium channels close, leaving the outward-flowing potassium channels as the only open channels. This causes rapid repolarization, dropping the voltage of the cell to – 90 mV and closing the currently open potassium channel. At the resting potential, the cell has only the original potassium channel slowly leaking potassium out of the cell, and we are returned to phase 4 of the action potential.

In summary, the 5 phases of the cardiac myocyte are as follows:

• Phase 4: Resting Potential at – 90 mV with minor depolarization from – 90 mV to – 70 mV; the passive outflow of potassium
• Phase 0: Rapid depolarization from – 70 mV to + 50 mV; inward VG sodium channels
• Phase 1: Minor repolarization; outward VG potassium channels
• Phase 2: Plateau at + 50 mV; outward VG potassium channels and inward VG calcium channels
• Phase 3: Repolarization from + 50 mV to – 90 mV; outward voltage-gated potassium channels

Cardiac Pacemaker Cell

The action potential for cardiac pacemaker cells (SA node, AV node, and Bundle of His/Purkinje Fibers) is unique to the AP of the general cardiac myocyte. These cells undergo automaticity and are responsible for the heart rate. Therefore, each AP corresponds to one beat of the heart and the inherent frequency of these cells is essential for maintaining proper rate control.

Additionally, the electrophysiology and anatomy of these pacemaker cells are discussed in a later section. We will use phases in line with the previous discussion of the cardiac myocyte; to explain, there are 3 basic phases of the pacemaker AP, but they are named phases 0, 3, and 4 correspondings with the phases of the myocyte action potential. The biggest difference to note in this AP is that calcium is the driving factor for rapid depolarization.

To begin, phase 4 involves sodium influx into the cell. This phase initiates at – 60 mV and the main ion influx is sodium. As the cell gains a positive charge due to the influx of positive ions, it reaches – 40 mV which is defined as the threshold for the pacemaker AP. As the voltage hits – 40 mV, voltage-gated calcium channels open into the cell to influx more positive ions. This influx of calcium ions denotes the beginning of phase 0, which is the action potential. The voltage continues to rise until it hits + 10 mV, which will shut off the voltage-gated calcium channels and open up voltage-gated potassium channels, which are efflux from the cell. The opening of the potassium channels begins phase 3 and the downslope of our voltage, and the voltage will drop back to the start of Phase 4 at – 60 mV where the potassium channels will close.

In summary, the 3 phases of the pacemaker action potential are as follows:

• Phase 4: Minor depolarization from – 60 mV to – 40 mV; passive inflow of sodium
• Phase 0: Rapid depolarization from – 40 mV to + 10 mV; inflow of VG calcium channels
• Phase 3: Repolarization from + 10 mV to – 60 mV; outflow of VG potassium channels

Lastly, each pacemaker cell has a different inherent rate at which it can maintain the heart. The SA node is responsible for heart rate under normal conditions; this means that the inherent rate of the SA node is typically around 60 to 100 beats per minute (BPM). The AV node is the second pacemaker which takes over rate if the SA node begins to fail; the AV node keeps the rate at 40 to 60 BPM. There are other foci situated around the SA and AV nodes (e.g., atrial foci and ventricular foci) that can contribute to the rate. In pathology such as atrial fibrillation, these Foci can even create a disease state through rapid firing which increases heart rate, but this discussion is out of scope for this article.

Electrophysiology

The electrical circuit of the heart follows a distinct pathway from the right atrium down throughout the ventricles of the heart. The electrical circuit begins at the Sinoatrial node, or SA node, which is located in the right atrium. This node is a unique bundle of cells that undergoes automaticity; these cells have their inherent rate of depolarization that is independent of other cells in the heart. As the SA node depolarizes, an electrical signal is simultaneously transmitted across from the right atrium to the left atrium via a bundle of cells termed “Bachman’s Bundle.” Following the SA node conduction, the current travels down to the Atrioventricular node, or AV node. The AV node is located further inferior in the Right Atrium by the interatrial septum. An important distinction to make about the AV node is that it creates a small pause in the electrical circuit. This pause is important because it delays the ventricles from contracting, and thus establishes successive contraction of the ventricles following the atria. If this pause did not occur, the atria and ventricles would contract simultaneously, and blood would not flow appropriately through the heart. The current leaves the AV node down a bundle of cells named the “Bundle of His” located inferior to the AV node in the interventricular septum. The Bundle of His then transmits the conduction down two bundle branches that arc throughout the two ventricles; specifically, these are named the right and left bundle branches. The right and left bundle branches have many fascicles that divide off and supply much of the ventricles. The main continuation of the right and left bundle branch is the Purkinje Fiber system, which is a set of many small branches arcing throughout the remaining ventricular space and supplying it with the electrical output. [rx][rx]

In summary, the order of flow through the electrical system is as follows:

• SA node and Bachman’s Bundle
• AV node
• Bundle of His
• Right and left bundle branches
• Purkinje Fibers

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 the 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:

• Adherens junctions, which anchor actin filaments to the cytoplasm of cardiomyocytes.
• Desmosomes, which bind adhesion proteins to the cytoskeleton within cells, thus connecting the cells.
• 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 the 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:

• An action potential, induced by the pacemaker cells in the sinoatrial (SA) and atrioventricular (AV) nodes, is conducted to contractile cardiomyocytes through gap junctions.
• 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.
• 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.
• The myosin head binds to ATP and pulls the actin filaments toward the center of the sarcomere, contracting the muscle.
• 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 the 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.

Myoglobin: The heme component of myoglobin, shown in orange, binds oxygen. Myoglobin provides a backup store of oxygen to muscle cells.

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.

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