Smooth Muscle and Cardiac Muscle

Introduction

• Smooth and cardiac muscles exhibit specialized mechanisms of contraction adapted for involuntary control. Their function depends on calcium regulation, autonomic and hormonal influences, and unique properties such as myosin phosphorylation, electrical variability, and adaptive plasticity rather than organized sarcomeres.

Smooth Muscles

• Smooth muscles are located in visceral organs and blood vessels.
• They lack organized cross-striations due to absence of regular sarcomere arrangement.
• Their activity is controlled by the autonomic nervous system and circulating hormones.
• The length–tension relationship is variable and not strictly linear.
• Smooth muscles exhibit high energy efficiency, maintaining contraction with minimal energy expenditure.
• This property supports sustained functions such as vascular tone and organ motility.
• Contraction is slow, sustained, and well suited for involuntary physiological processes.

Types of Smooth Muscles

• Smooth muscles are classified into single-unit and multiunit types based on functional organization.

Single-unit Smooth Muscle

• Fibers are interconnected by gap junctions, allowing electrical coupling.
• An action potential spreads rapidly across fibers, producing synchronized contraction.
• These muscles behave as a functional syncytium, acting as a single unit.
• They are widely distributed in visceral organs, hence called visceral smooth muscles.
• Common locations include the gastrointestinal tract, urinary bladder, ureters, uterus, and small blood vessels.
• Their coordinated activity is suitable for functions such as peristalsis and organ emptying.

Multiunit Smooth Muscle

• Fibers lack gap junctions, so each fiber contracts independently.
• These muscles do not function as a syncytium.
• They are richly supplied by the autonomic nervous system, allowing precise control.
• Their activity resembles skeletal muscle in terms of discrete fiber response, but remains involuntary.
• Examples include muscles of the iris and ciliary body, large airways, precapillary sphincters, and piloerector muscles.
• Multiunit smooth muscles enable fine regulation of tension and movement in specialized structures.

Functional Organization

• Smooth muscles perform diverse roles despite similar microscopic appearance.
• Their arrangement varies to meet specific functional requirements in different organs.

Circular Arrangement

• Fibers are arranged in a ring-like pattern around a lumen.
• Contraction reduces the diameter and regulates flow through the passage.
• This pattern is seen in blood vessels and airways.
• In sphincters, strong contraction can completely occlude the lumen.

Circular and Longitudinal Arrangement

• Two layers are present: inner circular and outer longitudinal fibers.
• Coordinated contraction produces peristalsis and mixing movements.
• This arrangement is typical of the gastrointestinal tract. It facilitates propulsion of contents along the digestive system.

Circular, Longitudinal, and Oblique Arrangement

• Three-layered organization allows powerful and multidirectional contraction.
• Found in organs such as the uterus and urinary bladder.
• Stretch of the organ triggers contraction to expel contents. Thus, structural arrangement of smooth muscle fibers determines their functional efficiency in regulating flow, propulsion, and emptying of hollow organs.

Structure

• Smooth muscle cells retain the ability to divide throughout life, unlike skeletal muscle fibers.
• The cells are small, allowing precise control of visceral functions.
• Each fiber is spindle-shaped, measuring about 100–300 micrometers in length and 5–10 micrometers in diameter.
• A single elongated nucleus is located centrally.
• Mitochondria are relatively few, and energy is largely derived from glycolysis.
• The sarcoplasmic reticulum is variably developed depending on muscle type.
• Myofilaments are arranged irregularly, without organized sarcomeres. Hence, striations are absent under light microscopy.
• There is no well-developed transverse tubular system.
• The cell membrane contains caveolae, which increase surface area and assist in calcium handling.
• These structural features support slow, sustained, and energy-efficient contraction.

Myofilaments

• The cytoplasm contains thick, thin, and intermediate filaments.
• A calcium-binding protein, calmodulin, regulates contraction in place of troponin.

Thick Filaments

• Thick filaments are composed of myosin and measure about 2.2 micrometers in length.
• They are fewer in number and arranged irregularly compared to skeletal muscle.
• They lie interspersed among thin filaments without a fixed pattern.

Intermediate Filaments and Dense Bodies

• Intermediate filaments are about 10 nanometers in diameter and provide structural support.
• They have minimal direct role in contraction.
• Dense bodies are electron-dense structures present within the cytoplasm and along the membrane.
• Membrane-associated dense bodies are also called focal adhesions.
• Dense bodies function similarly to Z lines by anchoring filaments.

Thin Filaments

• Thin filaments are composed of actin and tropomyosin.
• The troponin complex is absent, and regulation depends on calmodulin.

Organization of Filaments

• Filaments are loosely arranged without a regular geometric pattern.
• The length–tension relationship is therefore flexible.
• Filaments are oriented obliquely to the cell axis.
• Actin filaments attach to dense bodies through alpha-actinin.
• During contraction, sliding of filaments reduces the distance between dense bodies.
• Force is transmitted to the cell membrane, producing shortening and contraction of the muscle cell.

Organization of Muscle Fibers

• Smooth muscle fibers are arranged in sheets and interconnected by connective tissue.
• Collagen and elastin within a reticular framework provide structural support and continuity.
• Cells are linked by gap junctions, enabling rapid electrical communication.
• A single action potential can activate multiple cells simultaneously.
• Mechanical coupling through connective tissue ensures coordinated force transmission.
• Electrical and mechanical integration produces smooth, synchronized contraction across the tissue.

Innervations of Smooth Muscles

• Smooth muscles show spontaneous rhythmic activity, which is modulated by neural input.
• They are innervated by both sympathetic and parasympathetic divisions of the autonomic nervous system.
• Neurotransmitters are released from multiple varicosities along nerve fibers.
• These chemicals diffuse to nearby muscle cells rather than acting at a single synaptic site.
• Well-defined neuromuscular junctions are absent.
• Receptors for neurotransmitters are widely distributed on the cell membrane.
• This diffuse arrangement allows coordinated and graded responses of smooth muscle.

Electrical Properties

• Smooth muscle contraction may occur with or without a preceding action potential.
• These muscles respond to diverse stimuli, including neural, hormonal, chemical, thermal, and mechanical factors.
• Common stimuli include neurotransmitters, circulating hormones, hypoxia, increased hydrogen ion concentration, and stretch.

Characteristic Electrical Activities

• The membrane potential is variable, typically ranging from −30 to −70 millivolts, with an average near −50 millivolts.
• There is no stable resting membrane potential as seen in skeletal muscle.
• Excitatory stimuli reduce membrane potential, leading to depolarization.
• Inhibitory stimuli increase membrane potential, causing hyperpolarization.
• Visceral smooth muscle exhibits spontaneous rhythmic oscillations known as slow waves.
• Some oscillations reach threshold and generate action potentials.
• Multiunit smooth muscle usually does not show spontaneous activity and responds mainly to neural input. It is less sensitive to stretch compared to visceral smooth muscle.
• Action potentials vary in form, including single spikes, plateau-type potentials, or multiple spikes.
• In certain conditions, stimuli such as stretch or hormones produce graded potentials.
• These graded changes may summate and trigger action potentials.
• Overall, electrical activity in smooth muscle is adaptable and supports diverse physiological functions.

Action Potential

• Smooth muscle action potentials are of low amplitude (about 60 millivolts) and long duration (around 100 milliseconds).
• Depolarization occurs mainly due to calcium influx through voltage-gated calcium channels.
• The upstroke is slow because calcium channels open more gradually than sodium channels.
• Repolarization occurs due to closure of calcium channels.
• Opening of potassium channels contributes to the later phase of repolarization.
• Action potentials are commonly seen in visceral smooth muscle.
• Some smooth muscle cells can contract without significant membrane potential changes.

Junctional Potential

• ·  In multiunit smooth muscle, junctional potentials replace action potentials.
• ·  Neurotransmitters produce local depolarization that spreads passively along the cell membrane.
• ·  This depolarization promotes calcium entry and initiates contraction.

Pacemaker Potential

• ·  Pacemaker potentials are spontaneous rhythmic depolarizations in visceral smooth muscle.
• ·  They are not confined to a single site and can arise at multiple locations.
• ·  These potentials spread locally and regulate rhythmic contractile activity.

Mechanism of Contraction

Role of Calcium

• ·  Calcium ions are the primary regulators of smooth muscle contraction.
• ·  The strength of stimulus determines the degree of rise in cytosolic calcium and thus the force of contraction.
• ·  Cytosolic calcium increases mainly by influx from extracellular fluid and partly by release from intracellular stores.
• ·  Calcium levels decrease by binding to calmodulin, reuptake into sarcoplasmic reticulum, and extrusion from the cell.

Calcium Influx

• ·  Calcium enters through voltage-gated, ligand-gated, and leak channels.
• ·  A large concentration gradient favors rapid calcium entry when channels open.

Calcium Release

• Calcium is released from the sarcoplasmic reticulum by:

1. Inositol trisphosphate-mediated pathway via second messengers.
2. Calcium-induced calcium release, where incoming calcium triggers further release.

Binding of Calcium to Calmodulin

• Calcium binds to calmodulin, forming a complex that initiates contraction.
• This binding occurs significantly when intracellular calcium rises from 10⁻⁷ to 10⁻⁴ molar concentration.

Pumping Back of Calcium to the SR

• Calcium is pumped back into the sarcoplasmic reticulum by calcium adenosine triphosphatase.
• It is also extruded via sodium–calcium exchange and membrane calcium pumps.

Calcium Efflux

• Contraction occurs through cross-bridge cycling between actin and myosin.
• The mechanism resembles that of skeletal muscle but is regulated by calmodulin instead of troponin. Thus, smooth muscle contraction is graded, slow, and energy efficient.

Molecular Basis of Contraction

• Contraction begins with an increase in cytosolic calcium, mainly due to influx from extracellular fluid and partial release from intracellular stores.
• Calcium binds to calmodulin, forming a calcium–calmodulin complex.
• This complex activates myosin light chain kinase, a calcium-dependent enzyme.
• Activated myosin light chain kinase phosphorylates the regulatory light chains of myosin.
• This phosphorylation enhances myosin adenosine triphosphatase activity.
• The activated myosin head binds to actin, initiating cross-bridge formation.
• Hydrolysis of adenosine triphosphate provides energy for the power stroke, pulling actin filaments.
• During the power stroke, adenosine diphosphate and inorganic phosphate are released.
• Binding of a new adenosine triphosphate molecule causes detachment of myosin from actin.
• Subsequent hydrolysis of adenosine triphosphate re-energizes the myosin head for another cycle.
• The cycle continues as long as myosin remains phosphorylated and calcium levels remain elevated.
• The degree of contraction depends on the level of intracellular calcium.
• In smooth muscle, regulation occurs through myosin-linked control, unlike skeletal muscle where regulation is actin-linked.
• This mechanism enables slow, sustained, and energy-efficient contraction suitable for visceral functions.

Mechanism of Relaxation

• Relaxation occurs due to dephosphorylation of myosin light chains by myosin light chain phosphatase.
• This enzyme remains active during both contraction and relaxation.
• During contraction, kinase activity exceeds phosphatase activity, maintaining phosphorylated myosin.
• When cytosolic calcium decreases, calcium dissociates from calmodulin.
• This reduces kinase activity and allows phosphatase activity to predominate.
• Myosin becomes dephosphorylated and its adenosine triphosphatase activity declines.
• Cross-bridge cycling stops, leading to muscle relaxation. Thus, contraction and relaxation are regulated by calcium-dependent phosphorylation balance.

Phasic and Tonic Contractions:

• Smooth muscle shows phasic or tonic contractions, unlike skeletal muscle patterns.

Phasic Contraction

• Contraction is followed by complete relaxation.
• Calcium levels, phosphorylation, and cross-bridge activity return to baseline.
• Seen in organs requiring rhythmic activity, such as the gastrointestinal tract.

Tonic Contraction

• Contraction is sustained without full relaxation.
• Calcium and phosphorylation remain above resting levels but below peak.
• The latch-bridge mechanism maintains tension with minimal energy use.
• Tonic contractions are important for maintaining vascular tone and organ support.

Latch-Bridge Mechanism

• The latch state refers to sustained contraction with low energy consumption in smooth muscle. It occurs when myosin remains attached to actin despite dephosphorylation.
• Dephosphorylation by myosin light chain phosphatase does not immediately detach cross-bridges.
• Detachment occurs only when cytosolic calcium falls below a critical level.
• These persistent attachments are called latch-bridges.
• The rate of cross-bridge cycling slows, and bridges remain attached longer.
• This reduces adenosine triphosphate utilization, making contraction energy efficient.
• Sustained tension can be maintained for prolonged periods with minimal fatigue.
• The force of contraction can be finely regulated by adjusting calcium levels.
• Relaxation occurs when intracellular calcium decreases below approximately 10⁻⁷ molar concentration.

Properties of Smooth Muscle

• Visceral smooth muscles exhibit electrical, mechanical, and functional properties.
• Electrical properties include depolarization, slow waves, and action potentials coordinating contraction.
• Mechanical properties tone, plasticity, and stress relaxation for sustained contractions.

Table 29.1: Properties of smooth muscle.

Category	Key Properties
Morphological	Non-striated fibres; lack of troponin, T-tubules, and specialized neuromuscular junctions.
Electrical	Gap junctions enable syncytium; cells show excitability, unstable resting potential, and variable action potentials.
Mechanical	Exhibits tonus, plasticity, sustained slow contractions, length–tension and force–velocity relationships, and adaptive hypertrophy.

Contractile Response

• Visceral smooth muscle shows a slow, sustained contractile response after stimulation. The latent period is approximately 100–200 milliseconds. Contraction lasts 200–500 milliseconds or longer, and relaxation is also prolonged, extending several hundred milliseconds.
• The contraction develops gradually due to slow calcium influx and cross-bridge cycling. This enables efficient, energy-conserving force generation suitable for hollow organs.

Muscle Tone

• Muscle tone (tonus) refers to continuous, spontaneous partial contraction. It arises from intrinsic slow-wave electrical activity. This maintains basal tension without external stimulation.
• In arterioles, tone plays a critical role in regulating vascular resistance and maintaining arterial pressure with minimal energy expenditure.
• Multiunit smooth muscle generally lacks inherent tone because fibres function independently and require neural input.

Length–Tension Relationship

• The length–tension relationship in smooth muscle is highly variable and not directly proportional.
• When stretched, the muscle initially increases tension, followed by a gradual decline despite maintained stretch.
• This adaptive reduction in tension is termed plasticity, mediated by sustained cross-bridge attachment.
• In blood vessels, this property is called stress relaxation, which stabilizes pressure despite volume changes.
• In hollow organs such as the stomach, similar adaptation allows accommodation of large volumes with minimal rise in internal pressure.
• This phenomenon supports functions such as storage, propulsion, and controlled emptying of contents.

Force–Velocity Relationship

• The force–velocity relationship in smooth muscle differs from skeletal muscle. Contraction velocity is low because myosin adenosine triphosphatase activity is reduced and cross-bridge cycling is slow.
• Fewer active cross-bridges and prolonged attachment enhance force generation with minimal energy expenditure.
• Velocity decreases as load increases, but smooth muscle can maintain force over a wide range of lengths and loads.
• Intracellular calcium concentration regulates contraction in a graded manner. Variations in calcium levels alter cross-bridge phosphorylation, producing diverse force–velocity patterns under different stimuli.
• These properties enable sustained contractions in organs such as blood vessels and gastrointestinal tract.

Smooth Muscle Hypertrophy

• Smooth muscle hypertrophy involves an increase in cell size, often accompanied by hyperplasia, which is an increase in cell number.
• During pregnancy, estrogen promotes enlargement of uterine smooth muscle and connective tissue. Contractile proteins increase, and more gap junctions develop to improve coordinated contractions.
• Mechanical stretch from the growing fetus further stimulates myometrial growth.
• In chronic hypertension, persistent pressure load induces vascular smooth muscle hypertrophy and hyperplasia, leading to thickened vessel walls.
• Elevated sympathetic activity and circulating catecholamines enhance cellular growth through trophic effects.
• Angiotensin two promotes proliferation, whereas glucocorticoids inhibit it.
• Additional modulators, including serotonin and adenosine, influence growth responses.
• In obstructed hollow organs, sustained intraluminal pressure triggers muscular hypertrophy to overcome resistance.
• Urinary bladder enlargement in outlet obstruction is a typical example of adaptive smooth muscle growth.

Neural and Hormonal Influences

Autonomic Control

• Neural and hormonal influences regulate visceral smooth muscle by modifying intrinsic pacemaker activity and excitability. The final response depends on receptor subtype and intracellular signaling pathways.
• The autonomic nervous system exerts dual control through parasympathetic and sympathetic divisions. Their effects vary with tissue type and receptor distribution.
• Parasympathetic stimulation is generally excitatory and mediated by acetylcholine. It reduces membrane potential, increasing cellular excitability.
• Acetylcholine enhances the frequency of action potentials and augments both rhythmic and tonic contractions, especially in gastrointestinal smooth muscle. This effect occurs through activation of phospholipase C, leading to inositol trisphosphate formation and increased intracellular calcium release.
• Sympathetic stimulation is predominantly inhibitory and mediated by catecholamines such as norepinephrine. It increases membrane potential and suppresses spike activity, producing relaxation.
• Activation of alpha receptors promotes calcium removal from the cytoplasm, lowering intracellular calcium concentration and reducing contractile activity.
• Activation of beta receptors stimulates cyclic adenosine monophosphate formation via adenylyl cyclase. This enhances calcium sequestration within the sarcoplasmic reticulum.
• Reduced cytoplasmic calcium and inhibition of myosin light chain kinase decrease cross-bridge formation, resulting in relaxation.
• Multiunit smooth muscle lacks intrinsic tone and depends on autonomic input for precise, graded contraction.
• Hormonal factors can further modulate smooth muscle activity by altering receptor sensitivity and intracellular signaling.
• Overall, coordinated neural and hormonal regulation ensures appropriate motility, vascular tone, and organ function.

Table 29.2: Differences between skeletal, cardiac, and smooth muscles.

Feature	Skeletal Muscle	Cardiac Muscle	Smooth Muscle
Distribution	Attached to bones; enables body movement	Restricted to heart wall	Present in viscera, vessels, iris; includes single-unit and multiunit types
Structure	Striated, long cylindrical fibres; multinucleated	Striated, short branched cells; single nucleus	Non-striated, spindle-shaped cells; single nucleus
Sarcoplasmic Reticulum	Highly developed	Moderately developed	Poorly developed
Functional Syncytium	Absent	Present via intercellular connections	Present, especially in visceral type
Innervation	Somatic nervous system	Autonomic nervous system	Autonomic nervous system
Control	Voluntary; no intrinsic rhythm	Involuntary; intrinsic pacemaker activity	Involuntary; may show rhythmicity
Blood Supply and Oxygen Use	Moderate supply and oxygen demand	Rich supply with high oxygen consumption	Lower oxygen requirement
Resting Membrane Potential	Approximately −90 millivolts	Approximately −90 millivolts	Variable, about −30 to −50 millivolts
Action Potential	Short duration; rapid conduction	Prolonged duration with plateau phase	Variable pattern; slower conduction
Contraction Characteristics	Rapid onset; can summate; shows tetanus	Sustained contraction; no tetanus	Slow, prolonged contraction; tetanus possible
Excitation–Contraction Coupling	Rapid	Very rapid and efficient	Slow and sustained
Length–Tension Relation	Optimal length produces maximum force	Similar to skeletal muscle	Shows plasticity and adaptability
Fatigue	Occurs with prolonged activity	Highly resistant to fatigue	Fatigue is minimal
Energy Utilization	Primarily carbohydrates; also fats and proteins	Mainly fatty acids, also carbohydrates and ketones	Low energy demand; uses carbohydrates and fats

Hormonal Control

• Hormonal control regulates smooth muscle tone by altering intracellular signaling pathways and calcium dynamics.
• Nitric oxide is released from endothelial cells in response to shear stress. It diffuses into vascular smooth muscle and activates guanylyl cyclase.
• Increased cyclic guanosine monophosphate activates protein kinase, which enhances calcium sequestration, opens potassium channels, and reduces intracellular calcium, producing relaxation.
• Angiotensin two, vasopressin, and endothelin promote contraction through inositol trisphosphate–mediated calcium release.
• Adenosine induces relaxation by increasing cyclic adenosine monophosphate levels.
• These hormonal mechanisms ensure precise regulation of vascular tone and organ function.

Cardiac Muscle

• Cardiac muscle forms the contractile tissue of the heart and functions involuntarily. It is striated but exhibits several properties similar to smooth muscle.
• Individual cells are short, approximately 100 micrometers long and 15 micrometers wide, with a single central nucleus.
• Fibres are branched and interconnected, forming a continuous network.
• Intercalated discs join adjacent cells and provide strong mechanical attachment.
• These discs contain numerous gap junctions, enabling rapid electrical communication and coordinated contraction.
• Cardiac muscle behaves as a functional syncytium, organized into atrial and ventricular units connected by specialized conduction pathways.
• Each syncytium follows the all-or-none principle, ensuring uniform contraction.
• The tissue has a rich capillary supply, supporting high metabolic activity and continuous function.
• Cells contain abundant mitochondria and glycogen, reflecting high energy demand.
• The sarcoplasmic reticulum is well developed but works in conjunction with extracellular calcium influx.
• Cardiac muscle exhibits intrinsic rhythmicity due to pacemaker activity, allowing spontaneous contraction.
• These features enable efficient, synchronized pumping essential for maintaining circulation.