Medical School · Year 1 · Histology · includes a quiz and discussion video

Lecture 8: Muscle Tissue - Cardiac and Smooth

Unit 1.2: Histology and Basic Tissues

Learning Objectives

By the end of this lecture, students will be able to:

1. Compare and contrast the structural features of cardiac and smooth muscle with skeletal muscle
2. Describe the structure and function of intercalated discs in cardiac muscle
3. Explain the mechanisms of cardiac muscle contraction and its regulation
4. Describe the organization and function of the cardiac conduction system
5. Explain the mechanism of smooth muscle contraction and its regulation
6. Distinguish cardiac, smooth, and skeletal muscle in histological sections

Cardiac Muscle

Location and Function

Cardiac muscle is found exclusively in the heart, forming the myocardium—the muscular wall that generates the pumping force driving blood through the circulatory system. Unlike skeletal muscle, cardiac muscle contracts continuously throughout life, producing rhythmic contractions approximately 100,000 times per day without fatigue. This remarkable endurance reflects the specialized structural and metabolic features of cardiac muscle cells.

Cardiac muscle is under involuntary control; we cannot consciously initiate or stop cardiac contractions. However, the autonomic nervous system modulates heart rate and contractile force—sympathetic stimulation increases both, while parasympathetic (vagal) stimulation decreases heart rate. The intrinsic rhythmicity of cardiac muscle arises from specialized pacemaker cells rather than from nervous input, ensuring that the heart continues to beat even when denervated.

Structural Features

Cardiac muscle cells, called cardiomyocytes, differ significantly from skeletal muscle fibers in both size and organization. Individual cardiomyocytes are relatively small—approximately 80-100 micrometers in length and 15 micrometers in diameter—compared to skeletal muscle fibers that may be centimeters long. Each cardiomyocyte typically contains one or two centrally located nuclei, though occasional binucleated cells are common.

Cardiomyocytes branch and interconnect to form a complex three-dimensional network rather than running as isolated parallel fibers. Cells join end-to-end at specialized junctional complexes called intercalated discs, which appear as dark lines crossing the fibers at irregular intervals in histological sections. Like skeletal muscle, cardiac muscle is striated, displaying the characteristic pattern of A bands and I bands resulting from the organized arrangement of thick and thin filaments in sarcomeres. However, the striations are often less prominent than in skeletal muscle and may be obscured by the abundant cytoplasmic organelles.

The cytoplasm of cardiomyocytes reflects their intense metabolic demands. Mitochondria are extraordinarily abundant, occupying approximately 30-40% of the cell volume—far more than in skeletal muscle. This mitochondrial density ensures adequate ATP production for continuous contraction, relying primarily on oxidative metabolism of fatty acids. Myoglobin is present in high concentrations, giving cardiac muscle its red color and facilitating oxygen diffusion. Lipid droplets are prominent, representing stored fuel. Lipofuscin pigment, the yellow-brown "wear and tear" pigment resulting from lysosomal degradation of organelles, accumulates with age and may be quite prominent in elderly individuals.

Atrial cardiomyocytes contain a unique feature not found in ventricular cells: membrane-bound granules containing atrial natriuretic peptide (ANP). When the atria are stretched by increased blood volume, ANP is released into the bloodstream, promoting sodium excretion by the kidneys and thereby helping to regulate blood volume and pressure.

<image>Panel A: Cardiac muscle at 400x in longitudinal section showing multiple fibers running diagonally with clearly demonstrated branching pattern and cross-striations of A and I bands visible but less distinct than skeletal muscle. Panel B: Central oval nuclei visible in several cells with one binucleated cell indicated plus capillaries between fibers demonstrating rich vascular supply due to abundant mitochondria. Panel C: Intercalated discs appearing as dark irregularly step-like lines crossing fibers at cell boundaries more darkly stained than Z lines with higher magnification inset at 1000x showing characteristic step-like pattern. Panel D: Comparison inset at same magnification showing cardiac features of branching fibers, central nuclei, and intercalated discs versus skeletal features of parallel non-branching fibers, peripheral nuclei, and no intercalated discs with 50 micrometer main and 10 micrometer inset scale bars.</image>

Intercalated Discs

Intercalated discs are the specialized junctional complexes that connect adjacent cardiomyocytes at their ends. They are visible in light microscopy as dark transverse lines crossing the muscle fibers, typically at irregular intervals corresponding to the varying lengths of individual cells. In electron microscopy, intercalated discs reveal a complex, step-like structure with transverse portions (running perpendicular to the fiber axis) and lateral portions (running parallel to the fiber axis). This stepped configuration increases the surface area for cell-to-cell contact.

Components of Intercalated Discs

Intercalated discs contain three types of junctions, each serving distinct functions.

The fascia adherens is the principal component of the transverse portion of the intercalated disc. It is structurally and functionally similar to the adherens junctions of epithelial tissues but forms a broader continuous band rather than a discrete belt. The transmembrane proteins are N-cadherins (rather than E-cadherins found in epithelia), which connect to actin filaments intracellularly through alpha-actinin and vinculin. The fascia adherens anchors the thin filaments of terminal sarcomeres to the cell membrane, transmitting contractile force from one cell to the next. In effect, it functions as a specialized Z line at the cell boundary.

Desmosomes (macula adherens) are also located in the transverse portion of the intercalated disc. Like desmosomes elsewhere, they contain desmosomal cadherins (desmogleins and desmocollins) that link to intermediate filaments—in cardiac muscle, desmin filaments—through desmoplakin and other plaque proteins. Desmosomes provide strong mechanical adhesion, preventing cells from being pulled apart during the constant stress of contraction. Mutations in desmosomal proteins cause arrhythmogenic right ventricular cardiomyopathy, a condition in which cardiomyocytes detach and die, being replaced by fibro-fatty tissue.

Gap junctions are located primarily in the lateral portions of the intercalated disc. They are composed of connexin proteins (predominantly connexin 43 in ventricular muscle) that form hexameric connexons; aligned connexons from adjacent cells create channels allowing direct passage of ions and small molecules between cells. Gap junctions provide electrical coupling between cardiomyocytes, allowing the rapid spread of action potentials from cell to cell. This electrical coupling transforms the population of individual cells into a functional syncytium—a group of cells that contract in coordinated fashion as if they were a single unit.

<image>Panel A: Low-magnification electron micrograph of complete intercalated disc crossing between two cardiomyocytes showing characteristic step-like interdigitating pattern with transverse portions perpendicular to myofibrils and lateral portions parallel appearing electron-dense overall. Panel B: Schematic showing transverse segments with blue fascia adherens anchoring terminal Z lines and actin filaments plus red desmosomes as paired electron-dense plaques connected by brown desmin intermediate filaments looping into cytoplasm. Panel C: Lateral segments containing green gap junctions where cell membranes come into close apposition for electrical coupling with hexameric connexon inset showing sodium, potassium, and calcium ions passing through channels. Panel D: Molecular detail showing fascia adherens with N-cadherins connecting through vinculin and alpha-actinin to actin, desmosome cadherins connecting through plaque proteins to desmin, and function labels of mechanical attachment versus electrical coupling.</image>

Cardiac Muscle Contraction

Excitation-Contraction Coupling

The mechanism of excitation-contraction coupling in cardiac muscle shares fundamental principles with skeletal muscle but has important differences that have significant physiological and pharmacological implications.

Cardiac muscle possesses T-tubules that conduct action potentials into the cell interior, but their organization differs from skeletal muscle. In cardiac muscle, T-tubules are located at the level of the Z lines rather than at the A-I junction. Additionally, cardiac muscle has dyads rather than triads: each T-tubule is associated with only one terminal cisterna of the sarcoplasmic reticulum, not two. The SR of cardiac muscle is also less extensively developed than in skeletal muscle.

The most important difference concerns the source of calcium for contraction. In skeletal muscle, all calcium for contraction comes from the SR, released through mechanical coupling between T-tubule voltage sensors (DHPR) and SR ryanodine receptors (RyR1). In cardiac muscle, the action potential opens L-type calcium channels (dihydropyridine-sensitive voltage-gated calcium channels) in the T-tubule membrane, allowing calcium to enter the cell from the extracellular fluid. This entering calcium then triggers the opening of ryanodine receptors (RyR2) in the SR membrane, causing a much larger release of calcium from SR stores. This mechanism is called calcium-induced calcium release (CICR).

The steps of cardiac excitation-contraction coupling proceed as follows: The action potential propagates along the sarcolemma and down the T-tubules. Depolarization opens L-type calcium channels in the T-tubule membrane, allowing extracellular calcium to enter. The local rise in calcium concentration near the SR triggers opening of RyR2 channels, releasing a flood of calcium from the SR into the cytoplasm. Calcium binds to troponin C on the thin filaments, initiating cross-bridge cycling and contraction—the same mechanism as skeletal muscle.

Relaxation requires removal of calcium from the cytoplasm. In cardiac muscle, calcium is removed by two main pathways: the SR calcium ATPase (SERCA2a) pumps calcium back into the SR, and the sarcolemmal sodium-calcium exchanger (NCX) extrudes calcium to the extracellular fluid. Approximately 70% of calcium is returned to the SR, while 30% is extruded by NCX. Phospholamban (PLB) is a regulatory protein that normally inhibits SERCA2a; when PLB is phosphorylated (by protein kinase A during sympathetic stimulation), this inhibition is relieved, and SERCA activity increases.

Regulation of Cardiac Contraction

The autonomic nervous system modulates cardiac function without initiating contraction (which occurs intrinsically). Sympathetic stimulation, through β₁-adrenergic receptors, increases both heart rate (chronotropy) and contractile force (inotropy). The molecular mechanisms include phosphorylation of L-type calcium channels (increasing calcium entry), phosphorylation of phospholamban (relieving inhibition of SERCA and accelerating relaxation), and phosphorylation of troponin I (accelerating cross-bridge cycling). The net effect is faster, more forceful contractions with faster relaxation—essential for increased cardiac output during exercise.

Parasympathetic stimulation, through muscarinic (M2) receptors, primarily affects the pacemaker cells of the SA node and conduction tissue, slowing heart rate. Effects on ventricular contractility are minimal because parasympathetic innervation of ventricular muscle is sparse.

<image>Panel A: T-tubule invagination at Z line level adjacent to terminal cisterna of SR forming dyad structure with action potential propagating down T-tubule and red L-type calcium channels DHPR opening for extracellular calcium entry as small blue dots. Panel B: Trigger calcium binding and opening blue RyR2 channels in SR membrane releasing much larger calcium amount via CICR with calcium binding troponin on adjacent thin filaments initiating contraction. Panel C: Relaxation showing green SERCA2a pumps in SR membrane pumping calcium back into SR plus orange NCX exchangers in sarcolemma extruding calcium in exchange for sodium with 70% SERCA and 30% NCX pathway distribution. Panel D: Phospholamban regulation inset showing PLB inhibiting SERCA when dephosphorylated with inhibition relieved when phosphorylated by PKA plus CICR positive feedback loop diagram with arrows indicating calcium movements.</image>

Cardiac Conduction System

The heart contains specialized cardiomyocytes that form the conduction system, responsible for generating and rapidly distributing electrical impulses to coordinate contraction. Unlike ordinary working cardiomyocytes, these cells are specialized for electrical generation and conduction rather than forceful contraction.

Components

The sinoatrial (SA) node is located in the wall of the right atrium near the opening of the superior vena cava. It contains specialized pacemaker cells (P cells) that spontaneously depolarize and generate action potentials, making the SA node the heart's natural pacemaker. The normal intrinsic rate of the SA node is 60-100 beats per minute, modified by autonomic input. SA node cells are small and pale-staining, with few organized myofibrils.

The atrioventricular (AV) node is located in the interatrial septum near the tricuspid valve. It receives impulses from the atria (transmitted through ordinary atrial muscle) and delays them slightly before passing them to the ventricles. This delay (approximately 0.1 second) ensures that atrial contraction is complete before ventricular contraction begins. The AV node can serve as a backup pacemaker if the SA node fails, with an intrinsic rate of 40-60 beats per minute.

The bundle of His (atrioventricular bundle) emerges from the AV node and passes through the central fibrous body (the only electrical connection between atria and ventricles) into the interventricular septum. It divides into right and left bundle branches that descend along either side of the septum.

Purkinje fibers are the terminal branches of the conduction system, spreading from the bundle branches through the ventricular myocardium to deliver impulses to working cardiomyocytes. They are the largest cells in the conduction system, easily recognized histologically by their large size, pale-staining cytoplasm, and central clear zone with relatively few myofibrils. Their cytoplasm is rich in glycogen. Purkinje fibers conduct impulses rapidly (approximately 4 meters per second, faster than ordinary cardiomyocytes), ensuring near-simultaneous activation of the entire ventricular mass.

<image>Panel A: Heart cutaway anterior view showing yellow SA node in right atrial wall near superior vena cava with impulse spread waves through atrial myocardium and orange AV node at base of interatrial septum. Panel B: Bundle of His penetrating gray fibrous skeleton barrier entering interventricular septum with right bundle branch descending along right septum side and left bundle branch dividing into anterior and posterior fascicles plus Purkinje fibers spreading through ventricular walls. Panel C: SA node histology inset showing small pale P cells with scant cytoplasm and few myofibrils embedded in fibrous tissue with nearby atrial myocytes for comparison. Panel D: Purkinje fiber histology at 400x showing large subendocardial cells with pale-staining cytoplasm, central clear zone from abundant glycogen and few myofibrils, and peripheral myofibrils with numbered activation sequence steps and arrows.</image>

Smooth Muscle

Location and Function

Smooth muscle is found throughout the body in the walls of hollow organs and tubes, where it controls the movement of contents through its lumen and regulates the diameter of the passageway. Major locations include the gastrointestinal tract (propelling food through peristalsis), blood vessel walls (controlling blood flow and pressure), respiratory tract (controlling airway diameter), urinary tract (moving urine and controlling bladder emptying), reproductive tract (transport of ova, uterine contractions), and skin (arrector pili muscles raising hairs, myoepithelial cells around glands).

Smooth muscle is under involuntary control, regulated by the autonomic nervous system, circulating hormones, and local chemical factors. Its contractions are typically slow compared to skeletal muscle but can be sustained for prolonged periods with relatively low energy expenditure—essential for maintaining vascular tone and gastrointestinal motility.

Structural Features

Smooth muscle cells are spindle-shaped (fusiform), tapering to points at each end, quite different from the cylindrical shape of striated muscle cells. They are relatively small, typically 20-200 micrometers in length and 5-10 micrometers in diameter, though smooth muscle cells in the pregnant uterus can reach 500 micrometers as they hypertrophy. Each cell contains a single, centrally located nucleus that is elongated with tapered ends when the cell is relaxed but becomes compressed and corkscrew-shaped when the cell contracts.

Smooth muscle is not striated because its contractile proteins are not organized into the regular sarcomeric arrangement seen in cardiac and skeletal muscle. Actin and myosin are present but are arranged obliquely across the cell rather than in parallel register. In place of Z lines, smooth muscle contains dense bodies scattered throughout the cytoplasm and dense plaques at the cell membrane. Dense bodies are intracellular structures composed primarily of alpha-actinin (like Z lines) that anchor actin filaments. Dense plaques are similar structures at the sarcolemma that attach the contractile apparatus to the cell membrane and, through integrins, to the extracellular matrix. Intermediate filaments (primarily desmin, but also vimentin in vascular smooth muscle) connect dense bodies to dense plaques, transmitting force to the cell surface.

The sarcoplasmic reticulum of smooth muscle is much less developed than in striated muscle. Instead, the sarcolemma contains numerous small invaginations called caveolae that may serve some functions analogous to T-tubules—bringing extracellular calcium closer to the cell interior and containing calcium channels and signaling molecules.

<image>Panel A: Single spindle-shaped smooth muscle cell in longitudinal section with central elongated nucleus and thin red actin filaments running obliquely anchored at small dark intracellular dense bodies and dark membrane-associated dense plaques. Panel B: Thicker blue myosin filaments interdigitating with actin filaments plus green intermediate filaments connecting dense bodies to dense plaques forming cytoskeletal network with caveolae as small membrane invaginations and sparse SR. Panel C: Contraction schematic showing oblique arrangement causing cell shortening and thickening pulling dense plaques together with nucleus compressed into corkscrew shape. Panel D: Cross-section inset showing thin to thick filament ratio of approximately 15:1 without regular hexagonal arrangement plus dense body molecular composition inset showing alpha-actinin with actin filaments inserting from both sides.</image>

Smooth Muscle Organization

Smooth muscle is organized in two fundamentally different patterns that have important functional implications.

Single-Unit (Visceral) Smooth Muscle

Single-unit smooth muscle cells are electrically coupled through abundant gap junctions, allowing action potentials to spread from cell to cell. The tissue functions as a syncytium—when one cell contracts, the impulse spreads and adjacent cells contract as well, creating a coordinated wave of contraction. Some cells within single-unit smooth muscle have pacemaker activity, spontaneously generating electrical impulses (slow waves) that may trigger contractions; the interstitial cells of Cajal in the gastrointestinal tract serve this pacemaker function.

Single-unit smooth muscle is found in the gastrointestinal tract (where coordinated peristaltic waves propel contents), the uterus (where coordinated contractions are essential for childbirth), the ureters (peristalsis moving urine), and small blood vessels. Because cells contract as a unit, the nervous system does not need to innervate every cell; relatively sparse innervation can modulate the behavior of the entire mass of tissue.

Multi-Unit Smooth Muscle

Multi-unit smooth muscle cells act more independently. Gap junctions are sparse or absent, so electrical coupling is minimal. Each smooth muscle cell (or small group of cells) is separately innervated, allowing fine, graded control of contraction. Spontaneous pacemaker activity is absent; contractions occur only in response to neural or hormonal signals.

Multi-unit smooth muscle is found where fine control is required: the iris (controlling pupil size), the ciliary body (controlling lens shape for accommodation), large airways, large blood vessels, and the arrector pili muscles of skin. The arrangement allows different portions of the tissue to contract independently and to different degrees.

Organization in Hollow Organs

In many hollow organs, smooth muscle is arranged in layers with different orientations. Typically, an inner circular layer (fibers running circumferentially) and an outer longitudinal layer (fibers running along the organ's length) work together. Contraction of the circular layer narrows the lumen; contraction of the longitudinal layer shortens the segment. Coordinated, sequential contraction and relaxation of these layers produces peristalsis—waves of constriction that propel contents along the tube.

<image>Panel A: Single-unit smooth muscle in intestinal wall showing sheet of spindle-shaped cells in close contact with abundant green gap junction spots and differently colored interstitial cell of Cajal pacemaker with electrical impulse waves spreading cell to cell and sparse nerve varicosities affecting multiple cells for coordinated contraction. Panel B: Multi-unit smooth muscle in iris showing individual cells with minimal contact and few or no gap junctions with each cell receiving its own nerve terminal with varicosities confining electrical activity to individual cells for independent finely graded contraction. Panel C: Hollow organ wall cross-section showing layered smooth muscle arrangement with inner circular layer as small circles and outer longitudinal layer as spindles with diagram showing circular contraction narrowing lumen and longitudinal contraction shortening segment. Panel D: Peristalsis progression animation showing sequential coordinated contraction and relaxation of circular and longitudinal layers propelling contents along tube demonstrating functional integration.</image>

Smooth Muscle Contraction

Key Differences from Striated Muscle

Smooth muscle contraction differs fundamentally from striated muscle in its regulatory mechanism. The key differences are the absence of troponin (the calcium-binding protein that regulates striated muscle contraction), the use of calmodulin as the calcium sensor, and the requirement for myosin phosphorylation before cross-bridge cycling can occur.

Mechanism of Contraction

The sequence of smooth muscle contraction begins with a stimulus, which may be neural (autonomic neurotransmitters), hormonal (circulating hormones), paracrine (local chemical factors like nitric oxide), or mechanical (stretch).

The stimulus leads to an increase in cytoplasmic calcium concentration. Calcium may enter from the extracellular fluid through voltage-gated calcium channels (depolarization-triggered) or receptor-operated calcium channels (ligand-triggered), or it may be released from the sarcoplasmic reticulum through IP₃-gated channels (in response to phospholipase C activation and inositol trisphosphate production).

The rise in calcium triggers the regulatory cascade. Calcium binds to calmodulin, a ubiquitous calcium-binding protein. The calcium-calmodulin complex then binds to and activates myosin light chain kinase (MLCK), an enzyme that phosphorylates the regulatory light chain of myosin. Phosphorylation of the myosin light chain enables the myosin head to interact with actin—this is fundamentally different from striated muscle, where myosin is always capable of binding actin and regulation is through troponin-tropomyosin blocking of actin.

Once myosin is phosphorylated, cross-bridge cycling proceeds similarly to striated muscle: the myosin head binds actin, executes a power stroke, detaches upon ATP binding, and is re-cocked by ATP hydrolysis. The oblique arrangement of filaments causes the cell to shorten and thicken rather than simply shortening along one axis.

Relaxation

Relaxation occurs when calcium levels fall. As calcium is removed from the cytoplasm (by plasma membrane calcium ATPases, sodium-calcium exchangers, and SR calcium pumps), calcium dissociates from calmodulin, MLCK becomes inactive, and no new myosin light chains are phosphorylated. Myosin light chain phosphatase (MLCP) then dephosphorylates the myosin light chains that were previously phosphorylated. Dephosphorylated myosin cannot initiate new cross-bridge cycles, and the muscle relaxes.

The Latch State

Smooth muscle has a unique ability to maintain prolonged contraction with minimal ATP consumption through the "latch state." In this state, dephosphorylated myosin heads remain attached to actin for extended periods, maintaining tension without ongoing cross-bridge cycling. The latch state allows smooth muscle to maintain vascular tone, keep sphincters closed, or maintain any sustained contraction efficiently—a capability not present in striated muscle.

<image>Panel A: Contraction pathway showing stimulus from neural, hormonal, or stretch sources increasing calcium via voltage-gated channels, receptor-operated channels, or SR release via IP3 pathway then calcium binding calmodulin causing conformational change. Panel B: Calcium-calmodulin complex activating MLCK which phosphorylates myosin light chain MLC shown as phosphate addition enabling phosphorylated myosin to bind actin for cross-bridge cycling and contraction. Panel C: Relaxation pathway showing calcium decrease via PMCA pump, NCX exchange, and SR uptake causing calmodulin to release calcium and MLCK to become inactive then MLCP dephosphorylating MLC so myosin cannot bind actin. Panel D: Latch state box showing dephosphorylated cross-bridges remaining attached to actin maintaining tension with low ATP consumption plus Rho kinase ROCK regulation of MLCP for calcium sensitization and molecular diagrams of phosphorylated active versus dephosphorylated inactive myosin head.</image>

Smooth Muscle Regulation

Smooth muscle receives input from multiple regulatory systems, allowing complex integration of signals.

Neural Control

The autonomic nervous system provides neural control of smooth muscle, but the arrangement differs from the discrete motor end plates of skeletal muscle. Autonomic nerve fibers have varicosities—bead-like swellings along the axon that contain neurotransmitter-filled vesicles. When an action potential arrives, neurotransmitter is released from these varicosities and diffuses to nearby smooth muscle cells, affecting all cells within the diffusion range. This creates "diffuse junctions" rather than point-to-point connections, allowing one nerve fiber to influence many smooth muscle cells.

Sympathetic fibers typically release norepinephrine, which can cause either contraction or relaxation depending on the receptor type expressed: α₁-adrenergic receptors (Gq-coupled) cause contraction, while β₂-adrenergic receptors (Gs-coupled) cause relaxation. Parasympathetic fibers release acetylcholine, which acts on muscarinic receptors (M₃ in most smooth muscle) to cause contraction through the Gq-IP₃ pathway.

Hormonal and Paracrine Control

Circulating hormones influence smooth muscle throughout the body. Epinephrine from the adrenal medulla acts on adrenergic receptors. Angiotensin II is a potent vasoconstrictor. Oxytocin stimulates uterine contraction during labor and myoepithelial cell contraction during lactation.

Paracrine factors (locally released substances) are particularly important in blood vessels. Nitric oxide (NO), released from endothelial cells, is a potent vasodilator—it diffuses into adjacent smooth muscle and activates guanylyl cyclase, increasing cGMP and causing relaxation. Endothelin, also from endothelial cells, is a powerful vasoconstrictor. Prostaglandins, histamine, and many other local mediators affect smooth muscle tone in various tissues.

Stretch

Many smooth muscles respond to stretch with contraction (the myogenic response). Stretch opens stretch-activated cation channels or voltage-gated calcium channels, causing depolarization and calcium entry. This response is particularly important in blood vessels, where it helps maintain constant blood flow despite changes in perfusion pressure (autoregulation), and in the gastrointestinal tract, where distension triggers contraction.

Clinical Correlations

Cardiomyopathies

Cardiomyopathies are diseases of the heart muscle with diverse causes. Hypertrophic cardiomyopathy often results from mutations in sarcomeric proteins (beta-myosin heavy chain, myosin-binding protein C, troponins) and causes abnormal thickening of the ventricular wall, particularly the septum. Dilated cardiomyopathy, characterized by ventricular dilation and weakened contraction, has many causes including genetic mutations, viral infection, and toxic exposure. Arrhythmogenic right ventricular cardiomyopathy results from mutations in desmosomal proteins (desmoplakin, plakophilin, desmoglein); the resulting defective cell-cell adhesion leads to cardiomyocyte death and replacement by fibro-fatty tissue, creating substrates for dangerous arrhythmias.

Asthma

Asthma involves airway smooth muscle that is hyperresponsive to stimuli. Exposure to allergens, irritants, or other triggers causes bronchoconstriction—smooth muscle contraction narrowing the airway lumen. Treatment includes β₂-adrenergic agonists (such as albuterol), which relax airway smooth muscle by activating adenylyl cyclase, increasing cAMP, and inhibiting MLCK.

Hypertension

Hypertension (high blood pressure) involves abnormal vascular smooth muscle tone and, over time, structural remodeling of vessel walls. Increased smooth muscle contraction narrows arterioles, increasing peripheral resistance. Treatment targets include calcium channels (calcium channel blockers prevent calcium entry needed for contraction), adrenergic receptors (alpha blockers prevent norepinephrine-induced contraction; beta blockers reduce sympathetic drive), and the renin-angiotensin system (ACE inhibitors and ARBs reduce angiotensin II-mediated vasoconstriction).

Leiomyomas

Leiomyomas are benign tumors of smooth muscle. The most common site is the uterus, where they are called fibroids—affecting up to 70% of women by age 50. Uterine leiomyomas arise from myometrial smooth muscle and can cause heavy menstrual bleeding, pelvic pain, and fertility problems depending on their size and location. Leiomyomas can also occur in the gastrointestinal tract, skin, and other locations.

Summary

Cardiac muscle consists of branching, striated cells (cardiomyocytes) with one or two central nuclei. Cells are joined end-to-end by intercalated discs containing fascia adherens (mechanical attachment through actin), desmosomes (mechanical strength through intermediate filaments), and gap junctions (electrical coupling through connexins). The gap junctions create a functional syncytium, allowing coordinated contraction.

Cardiac excitation-contraction coupling differs from skeletal muscle through calcium-induced calcium release (CICR): extracellular calcium entering through L-type calcium channels triggers much larger calcium release from the SR via RyR2 channels. The autonomic nervous system modulates cardiac function through β₁-adrenergic (sympathetic, increasing rate and force) and muscarinic (parasympathetic, decreasing rate) receptors.

The cardiac conduction system generates and distributes electrical impulses: the SA node (pacemaker), AV node (delay), bundle of His, bundle branches, and Purkinje fibers (rapid ventricular activation). Purkinje fibers are large, pale cells with abundant glycogen and few myofibrils.

Smooth muscle consists of spindle-shaped, non-striated cells with single central nuclei. Contractile filaments attach to dense bodies (intracellular) and dense plaques (at the membrane) rather than sarcomeres. Smooth muscle contraction is regulated by calcium-calmodulin activation of MLCK, which phosphorylates myosin light chains to enable cross-bridge cycling. The latch state allows sustained contraction with minimal ATP consumption.

Smooth muscle is organized as single-unit (electrically coupled, functioning as syncytium) or multi-unit (independently controlled cells). It is regulated by autonomic nerves, circulating hormones, paracrine factors, and stretch.

Key Terms

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