Smooth Muscle and Cardiac Muscle

10.3.1 Smooth Muscle

Smooth muscle is involuntary and nonstriated. Smooth mus­cle is present mainly in the visceral organs, so this type of muscle is also known as visceral muscle.

Smooth muscle helps in many vital functions in the body like passage of food bolus in the digestive tract through peristalsis, elimination of execratory products through uri­nary system, and regulation of blood flow through the blood vessels. Smooth muscle is under the control of autonomic nervous system and endocrine system. Muscle cells are small and spindle shaped with one centrally located nucleus. No neuromuscular junction is present, and instead of that, varicosities help in the transmission of nerve impulse to the cells. The contraction and relaxation are slower than the skeletal muscle. In some organs, smooth muscles have pace­maker cells. Less energy is required for their contraction, and they become fatigue slowly.

10.3.1.1 CellularStructure

Smooth muscle fibers are small and spindle shaped with one centrally located nucleus (Fig. 10.17). The average diameter of fibers is 2-10 mm. The elasticity is more in smooth muscle than striated muscle. Elasticity is very important for visceral organs like urinary bladder. In smooth muscle, myofibrils are absent and thick and thin filaments are not arranged in sarco­mere pattern; that is why they are nonstriated.

Smooth muscle fibers contain three types of filaments, i.e., thick myosin filaments, thin actin filaments, and intermediate filaments. Thick myosin filaments are longer in smooth mus­cle than skeletal muscle. Thin filaments actin and tropomyo­sin are present, but troponin is absent. During contraction, calcium ions attach with calmodulin instead of troponin. The intermediate filaments do not directly participate in contrac­tion, and they only form part of cytoskeletal framework that supports cell shape.

Sarcoplasmic reticulum stores Ca²+ ions, which are essen­tial for contraction. Cells are usually arranged in sheets within muscle and organized into two layers (longitudinal and circular) of closely apposed fibers, which have essen­tially the same contractile mechanisms as skeletal muscle.

10.3.1.1.1 Structural Differences: Smooth Muscle with Striated Muscle

Smooth muscle is nonstriated, and myofibrils and sarcomeres are absent. Thick and thin filaments are not arranged like skeletal muscle. Thick filaments are scattered throughout sar­coplasm, whereas thin filaments are attached to dense bodies. T-tubule is absent. Loose network of sarcoplasmic reticulum is present in the cytoplasm. Troponin is not present in smooth muscle, and instead of troponin C calcium ions attach with calmodulin during contraction. In single-unit smooth muscle, muscle cells are attached with one another with gap junctions. Gap junction is an electrical junction, which helps in the transmission of nerve impulse from one cell to another. In smooth muscle, connective tissues never unite to form tendon. Thick and thin filaments are arranged in slightly diagonal chains, which are attached to the plasma membrane or dense bodies. During contraction, when action potential reaches the cells, thick and thin filaments slide past each other. In smooth muscle, neuromuscular junction is absent. Instead of neuro­muscular junction, varicosities help in the transmission of nerve impulse to the smooth muscle cells.

10.3.1.2 Types of Smooth Muscle

Smooth muscle can be broadly classified into single-unit smooth muscle and multiunit smooth muscle.

1. Single-unit smooth muscle: In single-unit smooth muscle, muscle cells are connected to each other through gap junctions (Fig. 10.18).

Through these gap junctions, action potential transmits from one cell to another.

Fig. 10.17 Smooth muscle tissue. (a) The cells are spindle shaped with a centrally located nucleus. Anatomy of a relaxed (b) and contracted (c) smooth muscle cell

Fig. 10.18 Single -unit smooth muscle and multiunit smooth muscle. (a) Innervations of a single-unit smooth muscle through varicosities. (b) Innervations of multiunit smooth muscle through varicosities

synchronous pattern from only one synaptic input, and action potential spreads to all the cells and contraction of all the cells occurs at a time like a functional syncytium. Single-unit smooth muscle is myogenic with pacemaker potentials.

2. Multiunit smooth muscle: In multiunit smooth muscle, each cell receives its own synaptic input through single varicosity (Fig. 10.18). This allows for the multiunit smooth muscle to have a much finer control. No gap junction is present. So, cells are not electrically connected and hence selective activation of muscle fibers occurs. Multiunit smooth muscle is neurogenic.

10.3.1.3 FunctionofSmoothMuscie

Smooth muscle is involved in the movement of different visceral organs and glands; thus, smooth muscle serves a variety of functions in the body.

The basic functions of smooth muscle are the following:

1. Smooth muscle in gastrointestinal tract helps in the move­ment of the food bolus through peristalsis.

2. The smooth muscles in blood vessels regulate the blood flow and blood pressure through vascular resistance.

3. In urinary system, smooth muscle regulates the urine flow and smooth muscle in urinary bladder regulates the micturition.

4. Smooth muscle of reproductive tract helps in gamete transport, and contraction of uterus helps in parturition.

5. The contraction of smooth muscle of air passages of respiratory tract regulates the diameter bronchiole and passage of air.

6. The contraction of integument causes piloerection and helps in shivering thermogenesis during cold stress.

7. The smooth muscles in eye regulate the dilation and constriction of the pupil and regulate the entry of light through pupil. Smooth muscles in eye also change the shape lens as required.

10.3.1.3.1 Innervations of Smooth Muscle

Smooth muscles are innervated by postganglionic autonomic neurons. In smooth muscle, neurotransmitter remains in varicosities. When an action potential reaches the varicosity through the axon the neurotransmitter releases from the varicosities and attached with the receptors on the plasma membrane of muscle fibers. In single-unit smooth muscle, the innervation is restricted to a few fibers in the muscle and action potential is transmitted from one cell to another through gap junctions.

10.3.1.3.2 Stimuli Initiate Smooth Muscle Contraction Different stimuli which influence the smooth muscle contrac­tion are the following:

1. The spontaneous electrical activity in the plasma mem­brane of the smooth muscle fiber

2. Release of neurotransmitter by autonomic neurons

3. Different hormones

4. Some local changes in the chemical composition like paracrine agents, acidity, oxygen, osmolarity, and ion concentrations of extracellular fluid surrounding the mus­cle fibers

5. Stretch

10.3.1.4 Mechanism of Smooth Muscle Contraction

When an action potential reaches the sarcolemma through the neurotransmitter released from the varicosities, it causes the depolarization of membrane of smooth muscle cell (Fig. 10.19).

The depolarization of membrane or activation of neuro­transmitter results in entry of Ca²⁺ ions through the L-type voltage-gated calcium channel located in the plasma mem­brane. This increase in Ca²⁺ ions stimulates the release of Ca²⁺ ions from sarcoplasmic reticulum by the way of ryanodine receptors and IP3.

This process is known as Ca-induced Ca release. Then the Ca²⁺ ions bind with calmodulin, which results in the activa­tion of calmodulin.

Now crossbridge cycling occurs, which leads to muscle tone. The ATPase activity is less in smooth muscle than in skeletal muscle. That is why the speed of contraction is slow in smooth muscle.

10.3.1.5 Mechanism of Smooth Muscle Relaxation Smooth muscle contraction ends with the dephosphorylation of myosin light chains.

Unlike skeletal muscle, the depolarization in smooth mus­cle occurs during its activation. That is why simply reducing calcium ion concentration will not produce the relaxation of smooth muscle. Here, myosin light-chain phosphate is responsible for dephosphorylation of myosin light chain, which ultimately leads to relaxation of smooth muscle.

In smooth muscle, action potentials are slower and they can last for a long time. This may be due to slow opening of calcium channels. Repolarization of smooth muscle is also slow as potassium channels are also slow to react. Some smooth muscle cells act as pacemaker cells and generate action potential. These types of cells are seen in the intestines. It has been seen that in some smooth muscles, they contract without any action potential.

In multiunit smooth muscle, action potentials generally do not occur. Like in smooth muscle, iris depolarization occurs by norepinephrine and ACh, which is known as junctional potential. These neurotransmitters cause the contraction of smooth muscle. The junctional potential results in an influx of calcium through L-type channels into the cell.

Sometimes, the neurotransmitters activate a G-protein, which activates phospholipase C generating IP3. IP3 then initiates the release of calcium from the sarcoplasmic reticulum. Smooth muscle contraction is required to last for a long time. If the contraction occurs like skeletal muscle, then the energy demand will be high for this type of sustained contraction and muscle will become fatigue as intracellular ATP is depleted.

But this phenomenon does not occur because of a special mechanism known as latch state, which allows the smooth muscle to maintain high tension at low energy consumption. The smooth muscle tone remains high even if there is decrease in myosin light-chain kinase.

10.3.2 CardiacMuscle

Cardiac muscle is only present in the heart. They are striated like skeletal muscle but involuntarily. Cardiac muscle is mainly controlled by autonomic nervous system and endo­crine glands. The pacemaker cells of heart generate action potential, and the heart beats rhythmically. Heart supplies blood through the body, and it is possible because of well- organized contraction of cardiac muscle cells.

Fig. 10.19 Mechanism of smooth muscle contraction. (1) Depolarization of cell membrane or activation of hormone/ neurotransmitter, (2) opening of L-type voltage-gated calcium channels, (3) calcium-induced calcium release from sarcoplasmic reticulum, (4) increased intracellular calcium level, (5) calcium binds with calmodulin, (6) activation of myosin light­chain kinase (MLCK), (7) phosphorylation of myosin light chain, (8) increase in myosin ATPase activity, (9) myosin-P binds actin, (10) crossbridge cycling leads to muscle tone

10.3.2.1 Basic Organization of Cardiac Muscle Cells

Like skeletal muscle, cardiac muscle is also striated, and the organizations of sarcomeres are also similar with actin and myosin filaments (Fig. 10.20). But some differences are also there in the structures and arrangement of the muscle fibers, which allow their coordinated function. The cells of cardiac muscle are smaller than the cells of skeletal muscle and exhibit branching. The cells are interconnected to each other by intercalated discs and form functional syncytia. Intercalated disc has two types of membrane junctions, i.e., desmosomes and gap junctions. Desmosomes are mechanical junctions between the cardiac muscle cells. Gap junctions are electrical junctions which connect one cell to another and allow the propagation of action potential between cells. Action potential is generated from the cardiac cells, and the electrical impulse spreads from one cell to another through the gap junction. So, all the cardiac cells become excited at a time and contract as a single syncytium. The thick and thin filaments are arranged like that of skeletal muscle, which gives a striated appearance. Repeated dark and light bands, i.e., A bands and I bands, are seen when viewed under

Fig. 10.20 Cardiac muscle tissue. (a) Cardiac muscle cells are branched and are interconnected to each other by intercalated discs. (b) Intercalated disc

electron microscope. The Z-lines are present at the lateral border of the sarcomere. Thin filaments are composed of actin, troponin, and tropomyosin. Thick filaments are made up of myosins, which extend from the center of the sarcomere towards the Z-lines. The amount of connective tissue is more in cardiac muscle than in the skeletal muscle. This high amount of connective tissue prevents not only muscle rup­ture, but also overstretching of the heart.

10.3.2.2 MechanismofContraction

Like that of skeletal muscle, cardiac muscle contraction is thin filament regulated, with an elevation in intracellular Ca²+ required to promote actin-myosin interaction (Fig. 10.21). Action potential transmits through the plasma membrane of cardiac contractile cells. Then it travels down to T-tubule. The action potential causes opening of plasma membrane L-type Ca²⁺ channel in the T-tubules. Ca²⁺ enters cytosol from T-tubules. Increase of cytosolic Ca²⁺ concentration leads to release of large amount of Ca²⁺ from SR through ryanodine release channels. This process is called Ca²⁺- induced Ca²⁺ release. Increase in cytosolic Ca²⁺ causes bind­ing of Ca²⁺ to troponin C.

This binding of Ca²⁺ with troponin C results in a confor­mational change in the troponin-tropomyosin complex, tropomyosin is removed from its position, and the active site on actin becomes exposed. Now myosin head binds with actin and crossbridge formation occurs like skeletal muscle. Thin filaments slide inward between thick filaments.

Cardiac muscle can regulate the rise in intracellular Ca²⁺ ions, and by this process, force of contraction is regulated. In heart, all the muscle cells are activated during contraction, so recruiting more muscle cells is possible.

Moreover, tetany of cardiac muscle cells would prevent any pumping action and thus be fatal. Consequently, the heart relies on different means of increasing the force of contrac­tion, including varying the amplitude of the intracellular transient Ca²⁺.

10.3.2.3 MechanismofRelaxation

In cardiac muscle, relaxation starts due to re-accumulation of Ca²⁺ by the SR through the action of the SR Ca²⁺ pump (SERCA). It plays an important role in the relaxation process and decreases the cytosolic Ca²⁺, but the process is more complex in cardiac muscle.

The refractory period in cardiac muscle is long, and the plateau phase is also prolonged. Because of these reasons, cardiac muscle never tetanizes.

10.3.2.4 CardiacMuscleMetabolism

Like skeletal muscle, myosin uses energy in the form of ATP during contraction. So, the ATP pool is continuously replenished. The source of this ATP is aerobic metabolism, including the oxidation of fats and carbohydrates. During ischemic condition, the creatine phosphate pool, which converts ADP to ATP, may decrease and like skeletal muscle the creatine phosphate pool is small.

10.3.2.5 Cardiac Muscle Hypertrophy

Regular exercise such as regular running causes hypertrophy of individual cardiac muscle cells, which ultimately results in increased heart size.

This is an example of “physiological hypertrophy,” and it is beneficial for the animal. In contrast to this, pathological hypertrophy is also seen. If heart is remaining in constant

Fig. 10.21 Mechanism of cardiac muscle contraction

chronic pressure overload, it may undergo either concentric left ventricular hypertrophy or dilated left ventricular hyper­trophy, with impaired functional consequences.

10.3.3 Muscular Disorders of Domestic Animals

Different diseases influence the typical structure and functions of muscle. Various infections, toxins, or congenital origin causes primary muscular dysfunctions, leading to com­plete paralysis, paresis, or ataxia. But the major cause of the muscular disorder is dysfunction of the nervous system, e.g., rhinopneumonitis, tetanus, protozoal myelitis, and canine distemper. Some disorders that affect the neuromuscular junction, like hypocalcemia, hypermagnesemia, and myasthenia gravis, can lead to muscular weakness, fatigue, and paralysis. Some antibiotics, toxins (e.g., venoms, botuli­num toxins, tetanus toxins), and some muscle-relaxing drugs also affect the neuromuscular junction. The disorder in mus­cle membrane and muscle fiber is known as myopathies. The disorders in muscle membrane may occur due to hereditary problems (e.g., congenital in goats, myotonia) or acquired (e.g., hypothyroidism, vitamin E and selenium deficiency, hypokalemia). In muscle fiber, various diseases happen, like polymyositis, muscular dystrophy, white muscle disease, and eosinophilic and myositis myopathy.

Muscle trauma is prevalent in the horse and may be from external or extreme activities leading to muscle rupture. In horses, fibrotic myopathy in the rear limb is a mechanical lameness caused due to the trauma and subsequent fibrosis or ossification of the muscle. Different laboratory tests, viz. determining serum enzyme levels, histopathological exami­nation, and electromyographic studies, are used to diagnose muscular diseases.

Learning Outcomes

• The muscle is a contractile tissue consisting of mus­cle cells or muscle fibers. Contraction of muscle fibers generates force, and that causes motion. Three types of muscles are there in the body, i.e., skeletal muscle, smooth muscle, and cardiac mus­cle. Skeletal muscles are mainly attached to bones, smooth muscle is present in the walls of visceral organs, and cardiac muscle is located in the heart.

• The skeletal muscle fibers have a long cylindrical structure with many nuclei located in the periphery. The active contractile unit of muscle is known as the sarcomere. Each myofibril contains several types of protein cells called myofilaments.

• During contraction, action potential propagates through the sarcolemma and travels down the T-tubules causing the sarcoplasmic reticulum to release Ca²+ ions. The myosin head then attaches to the binding site of the G-actin molecule, and the formation of crossbridges occurs. Muscle relaxation occurs when the release of the neurotransmitter stops at the neuromuscular junction.

• Smooth muscle fibers are tiny and spindle shaped with one centrally located nucleus. Smooth muscle fibers contain three types of filaments, i.e., thick myosin filaments, thin actin filaments, and interme­diate filaments. During contraction, calcium ions attach with calmodulin instead of troponin. The intermediate filaments do not directly participate in contraction, and they only form part of the cytoskel- etal framework that supports cell shape.

• Cardiac muscles are striated like skeletal muscle but involuntarily, mainly controlled by the autonomic ner­vous system and endocrine glands. The cardiac muscle cells are smaller than the cells of skeletal muscle and exhibit branching. The cells are interconnected by intercalated discs and form functional syncytia. Like skeletal muscle, cardiac muscle contraction is thin filament regulated, with an elevation in intracellular Ca²⁺ required to promote actin-myosin interaction.

Exercises

Objective

Q1. What is the layer of connective tissue that separates the muscle tissue into small sections?

Q2. What is the name of loose connective tissue that surrounds individual muscle fibers?

Q3. Where are the crossbridges involved in muscle contrac­tion located?

Q4. During smooth muscle contraction, Ca²+ is attached to which protein?

Q5. What is the zone’s name in the central portion of A band of skeletal muscle where thin filaments are absent?

Q6. Into what does the neuron release its neurotransmitter at the neuromuscular junction?

Q7. What type of muscle is found in the eyes’ irises and the blood vessels?

Q8. What is the function of varicosities?

Q9. What is a T-tubule?

Q10. What is titin?

Q11. What are the principal proteins of muscle contraction?

Q12. What is sarcomere?

Subjective Questions

Q1. What is rigor mortis?

Q2. What is muscle atrophy?

Q3. What is muscle hypertrophy?

Q4. What is muscle fatigue?

Q5. Differentiate between the single-unit and multiunit smooth muscle.

Q6. Differentiate between isotonic and isometric contraction.

Q7. Describe the energy sources for skeletal muscle contraction.

Q8. Describe the events of skeletal muscle contraction (flow diagrammatically).

Q9. Describe different types of skeletal muscle fibers.

Q10. Explain—Cardiac muscle cannot be tetanized in vivo.

Answer to Objective Questions

A1. Perimysium

A2. Endomysium

A3. On the myosin myofilaments

A4. Calmodulin

A5. H zone

A6. Synaptic cleft

A7. Multiunit smooth muscle

A8. Varicosities innervate the smooth muscle

A9. The T-tubules are an invagination of the muscle cell’s sarcolemma

A10. Titin is a molecular spring attached to thin filaments A11. Actin and myosin

A12. The sarcomere is the portion between two successive Z-lines

Keywords for the Answer to Subjective Questions

A1. The word rigor mortis came from two Latin words, i.e., “rigor” means “stiffness” and “mortis” means “of death.” Rigor mortis or postmortem rigidity of muscles is an important sign of animal death.

A2. Muscle atrophy is the decrease in the size of the muscle due to a reduction in muscle mass.

A3. Muscle hypertrophy is the increase in the size of the muscle due to increase in muscle mass.

A4. If a muscle is used exhaustively, then the muscle’s performance decreases progressively and mostly recovers after a period of rest. This phenomenon is known as muscle fatigue.

A5. In a single unit of smooth muscle, the muscle cells are connected through gap junctions. Through these gap junctions, action potential transmits from one cell to another.

Each cell receives its synaptic input through single varicosity in multiunit smooth muscle. No gap junction is present. So, cells are not electrically connected, and selective activation of muscle fibers occurs.

A6. Isotonic contraction: When the muscle length changes but the muscle tension remains unchanged, the contrac­tion is known as an isotonic contraction (tonic = ten­sion). Isotonic contraction is seen during walking, running, and different types of activities.

Isometric contraction: When the muscle’s tension increases but the muscle’s length remains the same, then the contraction is known as an isometric contrac­tion (iso = same, metric = length). In this type of contraction, muscle provides the force, but no move­ment occurs at the joint and muscle length remains unchanged.

A7. Sources for skeletal muscle contraction: (1) cytosolic stored ATP, (2) creatine phosphate, (3) glycolysis, and (4) aerobic or oxidative respiration.

A8. Events of skeletal muscle contraction: crossbridge for­mation; power stroke generation; crossbridge detach­ment; reactivation of myosin heads.

A9. Types of skeletal muscle fiber: (1) slow-twitch muscle fibers or type I muscle fibers; (2) fast-twitch muscle fibers or type II muscle fibers: type IIa muscle fibers, fast-twitch glycolytic (type IIX) fibers.

A10. Cardiac muscle cannot be tetanized due to the long refractory period of its action potential.

Further Reading

Allen DG, Lamb GD, Westerblad H (2008) Skeletal muscle fatigue: cellular mechanisms. Physiol Rev 88:287-332

Basmajian JV (1978) Muscle alive: their functions revealed by electro­myography. Williams & Wilkins

Bradley K (2012) Cunningham’s textbook of veterinary physiology, 5th edn. Elsevier

Cooper R (1980) EEG technology. Butterworths, London

Craig R, Padron R (2004) Molecular structure of the sarcomere. Chapter 7. In: Engel AG, Franzini-Armstrong C (eds) Myology, 3rd edn. McGraw-Hill, Inc., New York, pp 129-166

Frandson RD, Lee WW, Dee FA (2009) Anatomy and physiology of farm animals, 7th edn. Wiley-Blackwell

Goto M, Kawai M, Nakata M, Itamoto K, Miyata H, Ikebe Y, Tajima T, Wada N (2013) Distribution of muscle fibers in skeletal muscles of the cheetah (Acinonyxjubatus). Mamm Biol 78(2):127-133

Gunning P, O’Neill G, Hardeman E (2008) Tropomyosin-based regula­tion of the actin cytoskeleton in time and space. Physiol Rev 88:1-35

Klemm WR (1969) Animal electroencephalography. Academic, New York

Luna VM, Daikoku E, Ono F (2015) “Slow” skeletal muscles across vertebrate species. Cell Biosci 5:62

Reece WO (2015) Dukes’ physiology of domestic animals, 13th edn. Wiley Blackwell

Schiaffino S, Reggiani C (2011) Fiber types in mammalian skeletal muscles. Physiol Rev 91:1447-1531

Scott W, Stevens J, Binder-Macleod SA (2001) Human skeletal muscle fiber type classifications. Phys Ther 81:1810-1816

Smith RF (1978) Fundamentals of neurophysiology. Springer

Swenson MJ, Reece WO (2005) Duke’s physiology of domestic animals. Panima

Talbot J, Maves L (2016) Skeletal muscle fiber type: using insights from muscle developmental biology to dissect targets for susceptibility and resistance to muscle disease. Wiley Interdiscip Rev Dev Biol 5: 518-534

Wan JJ, Qin Z, Wang PY, Sun Y, Liu X (2017) Muscle fatigue: general understanding and treatment. Exp Mol Med 49:e384