Muscles Physiology

Muscle Overview

The three types of muscle tissue are skeletal, cardiac, and smooth
These types differ in structure, location, function, and means of activation

Muscle Similarities

Skeletal and smooth muscle cells are elongated and are called muscle fibers Muscle contraction depends on two kinds of myofilaments actin and myosin Muscle terminology is similar
Sarcolemma muscle plasma membrane Sarcoplasm cytoplasm of a muscle cell

Skeletal Muscle Tissue

Packaged in skeletal muscles that attach to and cover the bony skeleton
Has obvious stripes called striations

Is controlled voluntarily (i.e., by conscious control)

Contracts rapidly but tires easily Is responsible for overall body motility Is extremely adaptable and can exert forces ranging from a fraction of an ounce to over 70 pounds

Cardiac Muscle Tissue

Occurs only in the heart Is striated like skeletal muscle but is not voluntary Contracts at a fairly steady rate set by the hearts pacemaker Neural controls allow the heart to respond to changes in bodily needs

Smooth Muscle Tissue

Found in the walls of hollow visceral organs, such as the stomach, urinary bladder, and respiratory passages Forces food and other substances through internal body channels
It is not striated and is involuntary

Functional Characteristics of Muscle Tissue

Excitability, or irritability the ability to receive and respond to stimuli

Contractility the ability to shorten forcibly

Extensibility the ability to be stretched or extended Elasticity the ability to recoil and resume the original resting length

Muscle Function

Skeletal muscles are responsible for all locomotion

Cardiac muscle is responsible for coursing the blood through the body Smooth muscle helps maintain blood pressure, and squeezes or propels substances (i.e., food, feces) through organs Muscles also maintain posture, stabilize joints, and generate heat

Skeletal Muscle

Skeletal Muscle

Each muscle is a discrete organ composed of muscle tissue, blood vessels, nerve fibers, and connective tissue The three connective tissue sheaths are:
Endomysium fine sheath of connective tissue composed of reticular fibers surrounding each muscle fiber Perimysium fibrous connective tissue that surrounds groups of muscle fibers called fascicles
Epimysium an overcoat of dense regular connective tissue that surrounds the entire muscle

Skeletal Muscle

Figure 9.2 (a)

Skeletal Muscle: Nerve and Blood Supply

Each muscle is served by one nerve, an artery, and one or more veins

Each skeletal muscle fiber is supplied with a nerve ending that controls contraction
Contracting fibers require continuous delivery of oxygen and nutrients via arteries Wastes must be removed via veins

Skeletal Muscle: Attachments

Most skeletal muscles span joints and are attached to bone in at least two places When muscles contract the movable bone, the muscles insertion moves toward the immovable bone, the muscles origin Muscles attach:
Directly epimysium of the muscle is fused to the periosteum of a bone
Indirectly connective tissue wrappings extend beyond the muscle as a tendon or aponeurosis

Microscopic Anatomy of a Skeletal Muscle Fiber

Each fiber is a long, cylindrical cell with multiple nuclei just beneath the sarcolemma
Fibers are 10 to 100 m in diameter, and up to hundreds of centimeters long Each cell is a syncytium produced by fusion of embryonic cells

Microscopic Anatomy of a Skeletal Muscle Fiber

Sarcoplasm has numerous glycosomes and a unique oxygen-binding protein called myoglobin Fibers contain the usual organelles, myofibrils, sarcoplasmic reticulum, and T tubules

Myofibrils

Myofibrils are densely packed, rodlike contractile elements

They make up most of the muscle volume The arrangement of myofibrils within a fiber is such that a perfectly aligned repeating series of dark A bands and light I bands is evident

Myofibrils

Figure 9.3 (b)

Sarcomeres

The smallest contractile unit of a muscle

The region of a myofibril between two successive Z discs Composed of myofilaments made up of contractile proteins
Myofilaments are of two types thick and thin

Sarcomeres

Figure 9.3 (c)

Myofilaments: Banding Pattern

Thick filaments extend the entire length of an A band Thin filaments extend across the I band and partway into the A band Z-disc coin-shaped sheet of proteins (connectins) that anchors the thin filaments and connects myofibrils to one another

Myofilaments: Banding Pattern

Thin filaments do not overlap thick filaments in the lighter H zone M lines appear darker due to the presence of the protein desmin

Myofilaments: Banding Pattern

Figure 9.3 (c, d)

Ultrastructure of Myofilaments: Thick Filaments

Thick filaments are composed of the protein myosin Each myosin molecule has a rodlike tail and two globular heads
Tails two interwoven, heavy polypeptide chains
Heads two smaller, light polypeptide chains called cross bridges

Ultrastructure of Myofilaments: Thick Filaments

Figure 9.4 (a)(b)

Ultrastructure of Myofilaments: Thin Filaments

Thin filaments are chiefly composed of the protein actin

Each actin molecule is a helical polymer of globular subunits called G actin The subunits contain the active sites to which myosin heads attach during contraction Tropomyosin and troponin are regulatory subunits bound to actin

Ultrastructure of Myofilaments: Thin Filaments

Arrangement of the Filaments in a Sarcomere

Longitudinal section within one sarcomere

Sarcoplasmic Reticulum (SR)

SR is an elaborate, smooth endoplasmic reticulum that mostly runs longitudinally and surrounds each myofibril

Paired terminal cisternae form perpendicular cross channels

Functions in the regulation of intracellular calcium levels Elongated tubes called T tubules penetrate into the cells interior at each A bandI band junction T tubules associate with the paired terminal cisternae to form triads

Sarcoplasmic Reticulum (SR)

Figure 9.5

T Tubules

T tubules are continuous with the sarcolemma They conduct impulses to the deepest regions of the muscle These impulses signal for the release of Ca2+ from adjacent terminal cisternae

Triad Relationships

T tubules and SR provide tightly linked signals for muscle contraction

A double zipper of integral membrane proteins protrudes into the intermembrane space
T tubule proteins act as voltage sensors SR foot proteins are receptors that regulate Ca2+ release from the SR cisternae

Sliding Filament Model of Contraction

Thin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree In the relaxed state, thin and thick filaments overlap only slightly Upon stimulation, myosin heads bind to actin and sliding begins

Sliding Filament Model of Contraction

Each myosin head binds and detaches several times during contraction, acting like a ratchet to generate tension and propel the thin filaments to the center of the sarcomere As this event occurs throughout the sarcomeres, the muscle shortens

Skeletal Muscle Contraction

In order to contract, a skeletal muscle must:

Be stimulated by a nerve ending Propagate an electrical current, or action potential, along its sarcolemma

Have a rise in intracellular Ca2+ levels, the final trigger for contraction

Linking the electrical signal to the contraction is excitation-contraction coupling

Nerve Stimulus of Skeletal Muscle

Skeletal muscles are stimulated by motor neurons of the somatic nervous system
Axons of these neurons travel in nerves to muscle cells Axons of motor neurons branch profusely as they enter muscles Each axonal branch forms a neuromuscular junction with a single muscle fiber

Neuromuscular Junction

The neuromuscular junction is formed from:

Axonal endings, which have small membranous sacs (synaptic vesicles) that contain the neurotransmitter acetylcholine (ACh) The motor end plate of a muscle, which is a specific part of the sarcolemma that contains ACh receptors and helps form the neuromuscular junction

Though exceedingly close, axonal ends and muscle fibers are always separated by a space called the synaptic cleft

Neuromuscular Junction

Figure 9.7 (a-c)

Neuromuscular Junction

When a nerve impulse reaches the end of an axon at the neuromuscular junction:
Voltage-regulated calcium channels open and allow Ca2+ to enter the axon

Ca2+ inside the axon terminal causes axonal vesicles to fuse with the axonal membrane

Neuromuscular Junction

This fusion releases ACh into the synaptic cleft via exocytosis ACh diffuses across the synaptic cleft to ACh receptors on the sarcolemma

Binding of ACh to its receptors initiates an action potential in the muscle

Destruction of Acetylcholine

ACh bound to ACh receptors is quickly destroyed by the enzyme acetylcholinesterase

This destruction prevents continued muscle fiber contraction in the absence of additional stimuli

Action Potential

A transient depolarization event that includes polarity reversal of a sarcolemma (or nerve cell membrane) and the propagation of an action potential along the membrane

Role of Acetylcholine (Ach)

ACh binds its receptors at the motor end plate

Binding opens chemically (ligand) gated channels

Na+ and K+ diffuse out and the interior of the sarcolemma becomes less negative This event is called depolarization

Depolarization

Initially, this is a local electrical event called end plate potential

Later, it ignites an action potential that spreads in all directions across the sarcolemma

Action Potential: Electrical Conditions of a Polarized Sarcolemma

The outside (extracellular) face is positive, while the inside face is negative

This difference in charge is the resting membrane potential

Figure 9.8 (a)

Action Potential: Electrical Conditions of a Polarized Sarcolemma

The predominant extracellular ion is Na+ The predominant intracellular ion is K+ The sarcolemma is relatively impermeable to both ions
Figure 9.8 (a)

Action Potential: Depolarization and Generation of the Action Potential

An axonal terminal of a motor neuron releases ACh and causes a patch of the sarcolemma to become permeable to Na+ (sodium channels open)
Figure 9.8 (b)

Action Potential: Depolarization and Generation of the Action Potential

Na+ enters the cell, and the resting potential is decreased (depolarization occurs) If the stimulus is strong enough, an action potential is initiated
Figure 9.8 (b)

Action Potential: Propagation of the Action Potential

Polarity reversal of the initial patch of sarcolemma changes the permeability of the adjacent patch

Voltage-regulated Na+ channels now open in the adjacent patch causing it to depolarize
Figure 9.8 (c)

Action Potential: Propagation of the Action Potential

Thus, the action potential travels rapidly along the sarcolemma Once initiated, the action potential is unstoppable, and ultimately results in the contraction of a muscle
Figure 9.8 (c)

Action Potential: Repolarization

Immediately after the depolarization wave passes, the sarcolemma permeability changes

Na+ channels close and K+ channels open

K+ diffuses from the cell, restoring the electrical polarity of the sarcolemma
Figure 9.8 (d)

Action Potential: Repolarization

Repolarization occurs in the same direction as depolarization, and must occur before the muscle can be stimulated again (refractory period)

The ionic concentration of the resting state is restored by the Na+-K+ pump
Figure 9.8 (d)

Excitation-Contraction Coupling

Once generated, the action potential:

Is propagated along the sarcolemma Travels down the T tubules Triggers Ca2+ release from terminal cisternae

Ca2+ binds to troponin and causes:

The blocking action of tropomyosin to cease Actin active binding sites to be exposed

Excitation-Contraction Coupling

Myosin cross bridges alternately attach and detach Thin filaments move toward the center of the sarcomere Hydrolysis of ATP powers this cycling process Ca2+ is removed into the SR, tropomyosin blockage is restored, and the muscle fiber relaxes

Excitation-Contraction Coupling

Figure 9.9

Role of Ionic Calcium (Ca2+) in the Contraction Mechanism

At low intracellular Ca2+ concentration:

Tropomyosin blocks the binding sites on actin Myosin cross bridges cannot attach to binding sites on actin The relaxed state of the muscle is enforced
Figure 9.10 (a)

Role of Ionic Calcium (Ca2+) in the Contraction Mechanism

At higher intracellular Ca2+ concentrations:

Additional calcium binds to troponin (inactive troponin binds two Ca2+) Calcium-activated troponin binds an additional two Ca2+ at a separate regulatory site
Figure 9.10 (b)

Role of Ionic Calcium (Ca2+) in the Contraction Mechanism

Calcium-activated troponin undergoes a conformational change This change moves tropomyosin away from actins binding sites

Figure 9.10 (c)

Role of Ionic Calcium (Ca2+) in the Contraction Mechanism

Myosin head can now bind and cycle This permits contraction (sliding of the thin filaments by the myosin cross bridges) to begin

Figure 9.10 (d)

Sequential Events of Contraction

Cross bridge formation myosin cross bridge attaches to actin filament

Working (power) stroke myosin head pivots and pulls actin filament toward M line Cross bridge detachment ATP attaches to myosin head and the cross bridge detaches Cocking of the myosin head energy from hydrolysis of ATP cocks the myosin head into the high-energy state

Sequential Events of Contraction

Myosin head (high-energy configuration)

1 Myosin cross bridge attaches to

the actin myofilament Thin filament

Thick filament

ADP and Pi (inorganic phosphate) released

4 As ATP is split into ADP and Pi,

2 Working strokethe myosin head pivots and

cocking of the myosin head occurs

bends as it pulls on the actin filament, sliding it toward the M line

Myosin head (low-energy configuration)

3 As new ATP attaches to the myosin

head, the cross bridge detaches

Figure 9.11

Contraction of Skeletal Muscle Fibers

Contraction refers to the activation of myosins cross bridges (force-generating sites) Shortening occurs when the tension generated by the cross bridge exceeds forces opposing shortening Contraction ends when cross bridges become inactive, the tension generated declines, and relaxation is induced

Contraction of Skeletal Muscle (Organ Level)

Contraction of muscle fibers (cells) and muscles (organs) is similar The two types of muscle contractions are:
Isometric contraction increasing muscle tension (muscle does not shorten during contraction)
Isotonic contraction decreasing muscle length (muscle shortens during contraction)

Isotonic and Isometric Contractions

Motor Unit: The Nerve-Muscle Functional Unit

A motor unit is a motor neuron and all the muscle fibers it supplies
The number of muscle fibers per motor unit can vary from four to several hundred Muscles that control fine movements (fingers, eyes) have small motor units

Motor Unit: The Nerve-Muscle Functional Unit

Motor Unit: The Nerve-Muscle Functional Unit

Large weight-bearing muscles (thighs, hips) have large motor units

Muscle fibers from a motor unit are spread throughout the muscle; therefore, contraction of a single motor unit causes weak contraction of the entire muscle

Muscle Spindles

Are composed of 3-10 intrafusal muscle fibers that lack myofilaments in their central regions, are noncontractile, and serve as receptive surfaces Muscle spindles are wrapped with two types of afferent endings: primary sensory endings of type Ia fibers and secondary sensory endings of type II fibers These regions are innervated by gamma () efferent fibers Note: contractile muscle fibers are extrafusal fibers and are innervated by alpha () efferent fibers

Muscle Spindles

Figure 13.15

Operation of the Muscle Spindles

Stretching the muscles activates the muscle spindle

There is an increased rate of action potential in Ia fibers

Contracting the muscle reduces tension on the muscle spindle

There is a decreased rate of action potential on Ia fibers

Operation of the Muscle Spindles

Figure 13.16

Muscle Twitch

A muscle twitch is the response of a muscle to a single, brief threshold stimulus

The three phases of a muscle twitch are:

Latent period first few milliseconds after stimulation when excitationcontraction coupling is taking place
Figure 9.13 (a)

Muscle Twitch Period of contraction cross bridges actively form and the muscle shortens

Period of relaxation Ca2+ is reabsorbed into the SR, and muscle tension goes to zero

Figure 9.13 (a)

Graded Muscle Responses

Graded muscle responses are:

Variations in the degree of muscle contraction Required for proper control of skeletal movement

Responses are graded by:

Changing the frequency of stimulation Changing the strength of the stimulus

Muscle Response to Varying Stimuli

A single stimulus results in a single contractile response a muscle twitch

Frequently delivered stimuli (muscle does not have time to completely relax) increases contractile force wave summation

Figure 9.14

Muscle Response to Varying Stimuli

More rapidly delivered stimuli result in incomplete tetanus

If stimuli are given quickly enough, complete tetanus results

Figure 9.14

Muscle Response: Stimulation Strength

Threshold stimulus the stimulus strength at which the first observable muscle contraction occurs
Beyond threshold, muscle contracts more vigorously as stimulus strength is increased Force of contraction is precisely controlled by multiple motor unit summation This phenomenon, called recruitment, brings more and more muscle fibers into play

Stimulus Intensity and Muscle Tension

Figure 9.15 (a, b)

Treppe: The Staircase Effect

Staircase increased contraction in response to multiple stimuli of the same strength Contractions increase because:
There is increasing availability of Ca2+ in the sarcoplasm
Muscle enzyme systems become more efficient because heat is increased as muscle contracts

Treppe: The Staircase Effect

Figure 9.16

Smooth muscle

Smooth muscle

Nonstriated
Lack sarcomeres Thin filaments anchored to dense bodies

Involuntary

Structure of smooth muscle

Shape of muscle fiber spindle shaped 1-5 m in diameter 20-500 m in length A single nucleus present in the central thick portion. Sarcolemma (cell membrane). Cytoplasm appears homogenous without striations. Fewer mitochondria as compared to the skeletal muscle. Metabolism mostly glycolytic. Actin, Myosin & Tropomyosin but NO Troponin

Structure of smooth muscle

Dense bodies present attached to the cell membranes OR dispersed throughout the cell Dense bodies serve the same purpose as the Z-discs

Attached to the dense bodies are numerous numbers of Actin filaments

Interspersed between the actin filaments are Myosin filaments (their diameter twice as much as actin filaments) Usually, 5-10 times as many actin filaments as Myosin filaments

Smooth Muscle Tissue

Figure 10.23

Smooth Muscle

Innervated by autonomic nervous system (ANS) Visceral or unitary smooth muscle Only a few muscle fibers innervated in each group Impulse spreads through gap junctions Contracts as a unit Often autorhythmic Multiunit: Cells or groups of cells act as independent units Errector pili of skin and iris of eye

Functional characteristics of smooth muscle

Contract when calcium ions interact with calmodulin Activates myosin light chain kinase Functions over a wide range of lengths Plasticity Multi-unit smooth muscle cells are innervated by more than one motor neuron Visceral smooth muscle cells are not always innervated by motor neurons Neurons that innervate smooth muscle are not under voluntary control

Oblique arrangement of sarcomeres

Smooth Muscle Cell

Sidepolar cross-bridges
Myosin filaments have sidepolar cross-bridges
Bridges on one side hinge in one direction & on the other side in the opposite direction Allows myosin to pull an actin filament in one direction while simultaneously pulling it in the other direction on the other side Allow smooth muscle to contract 80% as compared to only 30 % in the skeletal muscle (force of contraction in skeletal muscle is limited because of the presence of the z-disc, against which the thick filament will abutt against and cannot move any further) Calcium Pump: pumps Ca back into the SR if present for relaxation to take place. But it is very slow so that duration of cont. is longer.

Structure of smooth muscle

Neuromuscular Junction: Does not occur in smooth muscleInstead the autonomic nerves make diffuse junctions that secrete NT into the matrix coating of smooth muscle a few micrometers away from the muscle fiber Also the axons supplying them do not have terminal buttons but varicosities on their terminal axons that contain the vesicles containing the NT Neurotransmitter (NT) Apart from Ach, norepinephrine can also be released Instead of synaptic clefts, smooth muscles have contact junctions

Excitation-Contraction Coupling

Single unit Multi unit

Classification of smooth muscles

MULTI-UNIT SINGLE UNIT 1. Muscles of visceral organs .e.g. GIT, uterus, ureters & some of the smaller blood vessels. 2. Form a sheet or bundles of tissue. 3. Cell membranes show gap junctions that allows AP to pass rapidly from cell to cell. 1. Iris & Ciliary body of the eye, large arteries, Piloerector muscles 2. Showing discrete, individual smooth muscle fibers. 3. Smooth muscle cells not electrically linked. Each muscle fiber innervated by a single nerve ending. NT itself can spread and lead to an AP.

4. AP spreads rapidly 4. Selective activation of each throughout the sheet of cells muscle fiber that can then cells contract as a single unit. contract independently of each other.

Single-Unit Muscle

Properties of Single-Unit Smooth Muscle

Gap junctions Pacemaker cells with spontaneous depolarizations Innervation to few cells

Graded Contractions
No recruitment

Vary intracellular calcium

Stretch Reflex
Relaxation in response to sudden or prolonged stretch

Tone = level of contraction without stimulation Increases/decreases in tension

Multi-Unit Muscle

Multi vs. Single-Unit Muscle

Comparisons Types of Muscle

Single muscle twitch Single muscle contraction (muscle twitch) develops more slowly & relaxes even more slowly longer sustained contraction without fatigue Advantage: This ability allows the walls of the organs to maintain tension with a continued load .e.g. urinary bladder filled with urine A TYPICAL SMOOTH MUSCLE HAS A TOTAL CONTRACTION TIME OF 1-3 SECONDS (about 30 times as long as single skeletal muscle contraction)

Single muscle twitch

Action potential
In the normal resting state, the membrane potential is about -50 to -60 mv. The AP of visceral smooth muscle is of 2 types: Typical spike potentials: (similar to skeletal muscles) -mostly seen in the unitary smooth muscles AP with Plateaus: Starts like a typical spike potential but repolarization delayed for several hundred to as many as 1000 msec -accounts for the prolonged contraction that occurs in certain organs

Action potential - Slow wave potentials

Without an external stimulus membrane potential is often associated with a basic slow wave rhythm. This is itself not an AP but a local property of the smooth muscle fibers. Cause: Waxing & waning of the pumping of Na ions Conductance of the ion channels increase & decrease rhythmically When the peak of the slow wave reaches about -35 mv, threshold is reached and an AP develops & leads to a contraction at peak of the slow waves an AP can occur Pacemaker waves

Slow wave potentials

Pacemaker potentials

When unitary (visceral) smooth m. is stretched, spontaneous AP is usually generated, because:

1. Normal slow potentials caused by stretch

2. Overall in membran negativity caused by stretch

Role of calcium Poorly developed SR Presence of small invaginations abut the SR which release Ca when AP reaches it. Smooth muscle contraction is highly dependent on Extracellular Calcium concentration The main source of Calcium ions in smooth muscle is to greater extent ECF and to a lesser extent SR as compared to the skeletal muscles where greatest source of Calcium is SR. Calcium plays the main role in the prolonged contraction process.

Smooth muscle contraction sequence

Binding of Ach to the receptors Increased Influx of Ca into the cell from the following sources: 1. ECF thru Ca channels 2. Ca released from SR 3. Stretch-activated Ca channels when memb. Deformed 4. Chemical-gated Ca channels by NT & hormones Ca binds to Calmodulin Ca-Calmodulin activates the enzyme: Myosin light chain kinase MLCK or simply Myosin kinase Phosphorylation of myosin, using energy & Pi from ATP Increased ATPase activity & binding of myosin to actin Contraction of smooth muscle

Smooth Muscle Contraction

Smooth muscle relaxation sequence

Dephosphorylation of Myosin by myosin phosphatase/ MLCP Decreases its ATP activity Ca removed from cytoplasm using Ca-Na antiport protein & Ca-ATPase Calmodulin releases Ca & uncomplexes from MK MK is phosphorylated by Protein kinase, inactivating it Relaxation OR sustained contraction

Smooth Muscle Relaxation

Latch system

It is a state in which the dephosphrylated myosin remains attached to actin for prolonged period of time. This produces sustained contraction without consuming ATP & thus enables the smooth muscle to sustain long-term maintenance of tone without fatigue. E.g. urinary bladder full of urine.