Muscles and Muscle Tissue PART A Muscle Overview

Muscles and Muscle Tissue PART A

Muscle Overview The three types of muscle tissue are skeletal, cardiac, and smooth ¡ Skeletal and smooth muscle cells are elongated and are called muscle fibers ¡ Muscle contraction depends on two kinds of myofilaments – actin and myosin ¡

Muscle Similarities ¡ Muscle terminology is similar l Sarcolemma – muscle plasma membrane l Sarcoplasm – cytoplasm of a muscle cell l Prefixes – myo, mys, and sarco all refer to muscle

Skeletal Muscle Tissue ¡ ¡ ¡ Packaged in skeletal muscles that attach to and cover the bony skeleton It is striated Is controlled voluntarily Contracts rapidly but tires easily Is responsible for all locomotion, posture, joint stabilization and heat generation

Cardiac Muscle Tissue Occurs only in the heart ¡ Is striated like skeletal muscle but involuntary ¡ Contracts at a fairly steady rate set by the heart’s pacemaker ¡

Smooth Muscle Tissue Found in the walls of hollow visceral organs ¡ Propels food and other substances through organs ¡ It is not striated and 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 ¡

Structure and Organization of Skeletal Muscle Table 9. 1 a

Structure and Organization of Skeletal Muscle

Skeletal Muscle ¡ Each muscle is a discrete organ composed of muscle tissue, blood vessels, nerve fibers, and connective tissue

Skeletal Muscle ¡ The three connective tissue sheaths are: l Endomysium – fine sheath of connective tissue surrounding each muscle fiber l Perimysium – fibrous connective tissue that surrounds groups of muscle fibers ¡ Fascicles

Skeletal Muscle l Epimysium ¡ A layer of fibrous 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 muscle’s insertion moves toward the immovable bone, the muscle’s origin ¡

Skeletal Muscle: Attachments ¡ Muscles attach: l Directly – epimysium of the muscle is fused to the periosteum of a bone l Indirectly – connective tissue wrappings extend beyond the muscle as a tendon or aponeurosis

Microscopic Anatomy of a Skeletal Muscle Fibers are 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 oxygenbinding protein called myoglobin ¡ Fibers contain the usual organelles, myofibrils, sarcoplasmic reticulum, and T tubules ¡

Skeletal muscle fibers Sarcoplasmic reticulum (modified ER) ¡ T-tubules and myofibrils aid in contraction l T-tubules are continuous with the sarcolemma and filled with extracellular fluid ¡

Sarcoplasmic Reticulum (SR) SR - smooth endoplasmic reticulum that mostly runs longitudinally and surrounds each myofibril l Terminal cisterna ¡ Terminal enlargement of the SR ¡ Functions in the regulation of intracellular calcium levels ¡

Sarcoplasmic Reticulum (SR) Figure 9. 5

T Tubules T tubules are continuous with the sarcolemma ¡ T tubule proteins act as voltage sensors ¡ They conduct impulses to the deepest regions of the muscle ¡ These impulses signal for the release of Ca 2+ from adjacent terminal cisternae ¡

T Tubules They penetrate into the cell’s interior at each A band–I band junction ¡ Filled with extracellular fluid ¡ Triad l Pair of terminal cisterna l T-tubule ¡

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 ¡ It goes from Z disc to Z disc ¡ Composed of thin (actin) and thick (myosin) myofilaments ¡

Sarcomeres Figure 9. 3 c

Sarcomere ¡ A bands l Formed by thin and thick filaments l M line ¡ Central part of the thick filament ¡ Protein that keeps the thick filaments together l H zone ¡ On each side of the M line ¡ Formed by thick filament l Zone of overlap ¡ Thin filament between thick filaments

Sarcomere I band l Formed by thin filaments l Z line ¡ actinin proteins that anchors the thin filaments ¡ Titin keep the thick and thin filaments aligned and prevents the muscle fiber from overstretching ¡ From Z line to Z line ¡

Titin Keep the thick and thin filaments aligned ¡ Prevents the muscle fiber from overstretching ¡ Helps the sarcomere to restore to resting length after contraction ¡ 30

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 tail and two globular heads l Tails – two interwoven, heavy polypeptide chains l Heads – two smaller, light polypeptide chains called cross bridges

Thick Filaments Figure 9. 4 a, b

Thin Filaments ¡ Thin filaments are chiefly composed of l G actin - globular subunits ¡ The G actin contain the active sites to which myosin heads attach during contraction

Thin Filaments Tropomyosin ¡ Double stranded protein that covers the active sites of the G protein l Troponin – composed of 3 globular subunits ¡ One subunit binds Ca ¡ One subunit binds to tropomyosin ¡ One subunit binds to G actin l

Ultrastructure of Myofilaments: Thin Filaments Figure 9. 4 c

Arrangement of the Filaments in a Sarcomere • Longitudinal section within one sarcomere Figure 9. 4 d

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: l Be stimulated by a nerve ending l Propagate an electrical current, or action potential, along its sarcolemma l Have a rise in intracellular Ca 2+ levels, the final trigger for contraction

Skeletal Muscle 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 ¡ Formed from: l Axonal endings whith synaptic vesicles that contain acetylcholine l 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

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: l Voltage-regulated calcium channels open and allow Ca 2+ to enter the axon l Ca 2+ 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 l ACh diffuses across the synaptic cleft to ACh receptors on the sarcolemma l Binding of ACh to its receptors initiates an action potential in the muscle l

Role of Acetylcholine (Ach) ACh binds its receptors at the motor end plate ¡ Binding opens chemically (ligand) gated channels that allows Na+ and K+ movements ¡ Na+ diffuses in, K+ diffuse out and the interior of the sarcolemma becomes less negative ¡

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 ¡

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 ¡

Muscles and Muscle Tissue PART B

Excitation-Contraction Coupling ¡ Once generated, the action potential: l Is propagated along the sarcolemma l Travels down the T tubules l Triggers Ca 2+ release from terminal cisternae

Excitation-Contraction Coupling Ca 2+ binds to troponin and causes ¡ Tropomyosin to expose the active site of G protein ¡

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 ¡ Ca 2+ is removed into the SR, tropomyosin blockage is restored, and the muscle fiber relaxes ¡

Neurotransmitter released diffuses across the synaptic cleft and attaches to ACh receptors on the sarcolemma. Axon terminal Synaptic cleft Synaptic vesicle Sarcolemma 1 ACh ACh T tubule Net entry of Na+ Initiates an action potential which is propagated along the sarcolemma and down the T tubules. Ca 2+ SR tubules (cut) Ca 2+ SR Ca 2+ 2 ADP Pi 6 Action potential in T tubule activates voltage-sensitive receptors, which in turn trigger Ca 2+ release from terminal cisternae of SR into cytosol. Ca 2+ 3 Ca 2+ 5 Ca 2+ Tropomyosin blockage restored, blocking myosin binding sites on actin; contraction ends and muscle fiber relaxes. Ca 2+ Calcium ions bind to troponin; troponin changes shape, removing the blocking action of tropomyosin; actin active sites exposed. Removal of Ca 2+ by active transport into the SR after the action potential ends. Ca 2+ 4 Contraction; myosin heads alternately attach to actin and detach, pulling the actin filaments toward the center of the sarcomere; release of energy by ATP hydrolysis powers the cycling process. Figure 9. 10

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 ¡

Myosin head (high-energy configuration) ADP Pi 1 Myosin head attaches to the actin myofilament, forming a cross bridge. Thin filament ATP hydrolysis ADP Thick filament Pi 2 Inorganic phosphate (Pi) generated in the previous contraction cycle is released, initiating the power (working) stroke. The myosin head pivots and bends as it pulls on the actin filament, sliding it toward the M line. Then ADP is released. 4 As ATP is split into ADP and Pi, the myosin head is energized (cocked into the high-energy conformation). ATP Myosin head (low-energy configuration) 3 As new ATP attaches to the myosin head, the link between myosin and actin weakens, and the cross bridge detaches. Figure 9. 12

Contraction of Skeletal Muscle Fibers Contraction – refers to the activation of myosin’s 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 ¡

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 Figure 9. 13 a

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 Twitch Cycle of contraction, relaxation produced by a single brief threshold stimulus ¡ There are three phases to a muscle twitch l Latent period l Period of contraction l Period of relaxation ¡

Phases of a Muscle Twitch • Latent period – first few msec after stimulus; EC coupling taking place • Period of contraction – cross bridges from; muscle shortens • Period of relaxation – Ca 2+ reabsorbed; muscle tension goes to zero Figure 9. 14 a

Muscle Twitch Comparisons Figure 9. 14 b

Treppe: The Staircase Effect Treppe l Repeated stimulation of the same strength after relaxation phase has been completed ¡ It causes increased contraction l There is increasing availability of Ca 2+ in the sarcoplasm l Muscle enzyme systems become more efficient because heat is increased as muscle contracts ¡

Treppe: The Staircase Effect Figure 9. 18

Graded Muscle Responses Graded muscle responses are: l Variations in the degree of muscle contraction according to the demand imposed on the muscle ¡ Responses are graded by: l Changing the frequency of stimulation l Changing the strength of the stimulus ¡

Changing the Frequency of Stimulation Repeated stimulation before relaxation phase has been completed will cause: ¡ Wave summation l Frequently delivered stimuli where muscle does not have time to completely relax l It increases contractile force ¡

Changing the Frequency of Stimulation Incomplete tetanus l More rapidly delivered stimuli than in wave summation. Only some muscle relaxation allowed ¡ Complete tetanus l If stimuli are given even more rapidly than in incomplete tetanus. No muscle relaxation allowed ¡ Figure 9. 15

Frequency of Stimulation

Changing the Strength of Stimulation Threshold stimulus – the stimulus strength at which the first muscle contraction occurs ¡ Multiple motor unit summation or recruitment ¡ Muscle contracts more vigorously as stimulus strength is increased ¡ It brings more and more muscle fibers into play ¡

Threshold and Recruitment Figure 9. 16

Size Principle Figure 9. 17

Muscle Tone ¡ Muscle tone: l Is the constant, slightly contracted state of all muscles, which does not produce active movements l Keeps the muscles firm, healthy, and ready to respond to stimulus l Keeps posture l Stabilizes bones and joints

Muscle Tone ¡ Spinal reflexes account for muscle tone by: l Activating one motor unit and then another l Responding to activation of stretch receptors in muscles and tendons

Isotonic Contractions Isotonic contractions l The muscle changes in length l Once tension is sufficient to move the load it will stay the same ¡ Types of isotonic contractions l Concentric contractions – the muscle shortens because the muscle tension is greater than the load ¡

Isotonic Contractions Eccentric contractions – the muscle elongates because the peak tension developed is less than the load l The muscle elongates because ¡ the contraction of opposing muscles or ¡ the gravity l

Isotonic Contractions Figure 9. 19 a

Isometric Contractions ¡ Isometric Contractions l Tension increases to the muscle’s capacity, but the muscle neither shortens nor lengthens l Occurs if the load is greater than the tension the muscle is able to develop

Isometric Contractions Figure 9. 19 b

Muscle Metabolism: Energy for Contraction ATP is the only source used directly for contractile activity ¡ As soon as available stores of ATP are hydrolyzed (4 -6 seconds), they are regenerated by: l The interaction of ADP with creatine phosphate (CP) l Aerobic respiration l Anaerobic glycolysis ¡

Muscle Contraction requires large amounts of energy Immediate energy l ATP + Creatine = ADP + creatine phosphate l Creatine phosphate releases stored energy to convert ADP to ATP ¡ Aerobic metabolism provides most ATP needed for contraction l Long-term energy l Krebs cycle in mitochondria ¡

Muscle Metabolism: Energy for Contraction Figure 9. 20

Muscle Contraction requires large amounts of energy ¡ ¡ Anaerobic metabolism When muscle contractile activity reaches 70% of maximum: l Bulging muscles compress blood vessels l Oxygen delivery is impaired l Pyruvic acid is converted into lactic acid

Muscle Contraction requires large amounts of energy ¡ ¡ The lactic acid: l Diffuses into the bloodstream l Is picked up and used as fuel by the liver, kidneys, and heart l Is converted back into pyruvic acid by the liver Short-term energy

Muscle Fatigue The muscle is in a state of physiological inability to contract ¡ Muscle fatigue occurs when: l ATP production fails to keep pace with ATP use l There is a relative deficit of ATP, causing contractures l Lactic acid accumulates in the muscle l Ionic imbalances are present ¡

Muscle Fatigue Intense exercise produces rapid muscle fatigue (with rapid recovery) ¡ Na+-K+ pumps cannot restore ionic balances quickly enough ¡ Low-intensity exercise produces slow-developing fatigue ¡ SR is damaged and Ca 2+ regulation is disrupted ¡

Muscles and Muscle Tissue PART C

Oxygen Debt ¡ Oxygen debt – the extra amount of O 2 needed for the above restorative processes

Oxygen Debt Vigorous exercise causes dramatic changes in muscle chemistry ¡ For a muscle to return to a resting state: l Oxygen reserves must be replenished l Lactic acid must be converted to pyruvic acid l Glycogen stores must be replaced l ATP and CP reserves must be resynthesized ¡

Heat Production During Muscle Activity Only 40% of the energy released in muscle activity is useful as work ¡ The remaining 60% is given off as heat ¡ Dangerous heat levels are prevented by radiation of heat from the skin and sweating ¡

Force of Muscle Contraction ¡ The force of contraction is affected by: l The number of muscle fibers contracting – the more motor fibers in a muscle, the stronger the contraction l The relative size of the muscle – the bulkier the muscle, the greater its strength

Force of Muscle Contraction l Degree of muscle stretch – muscles contract strongest when muscle fibers are 80 -120% of their normal resting length

Force of Muscle Contraction Figure 9. 21 a–c

Length Tension Relationships Figure 9. 22

Muscle Fiber Type: Functional Characteristics Speed of contraction – determined by speed in which ATPases split ATP ¡ ATP-forming pathways l Oxidative fibers – use aerobic pathways l Glycolytic fibers – use anaerobic glycolysis ¡ These two criteria define three categories – slow oxidative fibers, fast oxidative fibers, and fast glycolytic fibers ¡

Fast versus Slow Fibers Figure 10. 21

Slow oxidative fibers Half the diameter of fast fibers ¡ Take three times as long to contract after stimulation ¡ Abundant mitochondria l aerobic metabolism ¡ Extensive capillary supply ¡ High concentrations of myoglobin ¡ Fatigue resistant ¡ Red color ¡

Fast glycolytic fibers Large in diameter ¡ Contain densely packed myofibrils ¡ Large glycogen reserves ¡ Relatively few mitochondria ¡ Produce rapid, powerful contractions of short duration ¡ Fast fatigue ¡ White color ¡

Fast oxidative or Intermediate fibers Similar to fast fibers ¡ Greater resistance to fatigue ¡ Pink color ¡ Intermediate glycogen storage ¡ many mitochondria ¡ Many capillaries ¡ Uses mainly aerobic metabolism ¡

Load and Contraction Figure 9. 23

Effects of Aerobic Exercise ¡ Aerobic exercise results in an increase of: l Muscle capillaries l Number of mitochondria l Myoglobin synthesis l Mainly in slow oxidative fibers l Not significant muscle hypertrophy

Effects of Resistance Exercise ¡ Resistance exercise (typically anaerobic) results in: l Muscle hypertrophy l Increased mitochondria, myofilaments, and glycogen stores l Increases muscle fibers

The Overload Principle Forcing a muscle to work promotes increased muscular strength ¡ Muscles adapt to increased demands ¡ Muscles must be overloaded to produce further gains ¡

Smooth Muscle Composed of spindle-shaped fibers with a diameter of 2 -10 m and lengths of several hundred m ¡ Lack the coarse connective tissue sheaths of skeletal muscle, but have fine endomysium ¡ Organized into two layers (longitudinal and circular) of closely apposed fibers ¡

Smooth Muscle Found in walls of hollow organs (except the heart) ¡ Have essentially the same contractile mechanisms as skeletal muscle ¡

Smooth Muscle Figure 9. 24

Peristalsis When the longitudinal layer contracts, the organ dilates and shorten ¡ When the circular layer contracts, the organ elongates and constrict ¡ Peristalsis – alternating contractions and relaxations of smooth muscles that mix and squeeze substances through the lumen of hollow organs ¡

Innervation of Smooth Muscle Smooth muscle lacks neuromuscular junctions ¡ Innervating nerves have bulbous swellings called varicosities ¡ Varicosities release neurotransmitters into wide synaptic clefts called diffuse junctions ¡

Innervation of Smooth Muscle Figure 9. 25

Microscopic Anatomy of Smooth Muscle ¡ ¡ ¡ SR is less developed than in skeletal muscle and lacks a specific pattern T tubules are absent Plasma membranes have pouchlike infoldings called caveoli

Microscopic Anatomy of Smooth Muscle Ca 2+ is sequestered in the extracellular space near the caveoli, allowing rapid influx when channels are opened ¡ There are no visible striations and no sarcomeres ¡ Thin and thick filaments are present ¡

Proportion and Organization of Myofilaments in Smooth Muscle Ratio of thick to thin filaments is much lower than in skeletal muscle ¡ Thick filaments have heads along their entire length ¡ There is no troponin complex ¡

Proportion and Organization of Myofilaments in Smooth Muscle Thick and thin filaments are arranged diagonally, causing smooth muscle to contract in a corkscrew manner ¡ Noncontractile intermediate filament bundles attach to dense bodies (analogous to Z discs) at regular intervals ¡

Smooth Muscle

Proportion and Organization of Myofilaments in Smooth Muscle Figure 9. 26

Contraction of Smooth Muscle Whole sheets of smooth muscle exhibit slow, synchronized contraction ¡ They contract in unison, reflecting their electrical coupling with gap junctions ¡ Action potentials are transmitted from cell to cell ¡

Contraction of Smooth Muscle ¡ Some smooth muscle cells: l Act as pacemakers and set the contractile pace for whole sheets of muscle l Are self-excitatory and depolarize without external stimuli

Contraction Mechanism Actin and myosin interact according to the sliding filament mechanism ¡ The final trigger for contractions is a rise in intracellular Ca 2+ ¡ Ca 2+ is released from the SR and from the extracellular space ¡ Ca 2+ interacts with calmodulin and myosin light chain kinase to activate myosin ¡

Contraction Mechanism Ca 2+ binds to calmodulin and activates it ¡ Activated calmodulin activates the kinase enzyme ¡ Activated kinase transfers phosphate from ATP to myosin cross bridges ¡ Phosphorylated myosin heads form cross bridges with actin ¡

Contraction Mechanism Power stroke is executed ¡ Smooth muscle relaxes when intracellular Ca 2+ levels drop ¡

Figure 9. 27

Special Features of Smooth Muscle Contraction ¡ Unique characteristics of smooth muscle include: l Smooth muscle tone l Slow, prolonged contractile activity l Low energy requirements l Response to stretch

Response to Stretch ¡ Smooth muscle exhibits a phenomenon called stress-relaxation response in which: l Smooth muscle responds to stretch only briefly, and then adapts to its new length l The new length, however, retains its ability to contract l This enables organs such as the stomach and bladder to temporarily store contents

Hyperplasia Certain smooth muscles can divide and increase their numbers by undergoing hyperplasia ¡ This is shown by estrogen’s effect on the uterus l At puberty, estrogen stimulates the synthesis of more smooth muscle, causing the uterus to grow to adult size ¡

Types of Smooth Muscle: Single Unit ¡ The cells of single-unit smooth muscle, commonly called visceral muscle: l Contract rhythmically as a unit l Are electrically coupled to one another via gap junctions l Often exhibit spontaneous action potentials l Are arranged in opposing sheets and exhibit stress-relaxation response

Types of Smooth Muscle: Multiunit ¡ Multiunit smooth muscles are found: l In large airways to the lungs l In large arteries l In arrector pili muscles l In the intrinsic eye muscles

Types of Smooth Muscle: Multiunit ¡ Their characteristics include: l Rare gap junctions l Infrequent spontaneous depolarizations l Structurally independent muscle fibers l A rich nerve supply, which, with a number of muscle fibers, forms motor units l Graded contractions in response to neural stimuli - recruitment

Table 9. 3. 3

Table 9. 3. 4

Developmental Aspects ¡ ¡ ¡ Muscle tissue develops from embryonic mesoderm called myoblasts Multinucleated skeletal muscle cells form by fusion of myoblasts l Syncytium The growth factor agrin stimulates the clustering of ACh receptors at newly forming motor end plates

Developmental Aspects ¡ ¡ As muscles are brought under the control of the somatic nervous system, the numbers of fast and slow fibers are also determined Cardiac and smooth muscle myoblasts do not fuse but develop gap junctions at an early embryonic stage

Developmental Aspects: Regeneration Cardiac and skeletal muscle become amitotic, but can lengthen and thicken ¡ Myoblastlike satellite cells show very limited regenerative ability ¡ Cardiac cells lack satellite cells ¡ Smooth muscle has good regenerative ability ¡

Developmental Aspects: After Birth Muscular development reflects neuromuscular coordination ¡ Development occurs head-to-toe, and proximal-to-distal ¡ Peak natural neural control of muscles is achieved by midadolescence ¡ Athletics and training can improve neuromuscular control ¡

Developmental Aspects: Male and Female There is a biological basis for greater strength in men than in women ¡ Women’s skeletal muscle makes up 36% of their body mass ¡ Men’s skeletal muscle makes up 42% of their body mass ¡

Developmental Aspects: Male and Female These differences are due primarily to the male sex hormone testosterone ¡ With more muscle mass, men are generally stronger than women ¡

Developmental Aspects: Age Related With age, connective tissue increases and muscle fibers decrease ¡ Muscles become stringier and more sinewy ¡ By age 80, 50% of muscle mass is lost (sarcopenia) ¡

Developmental Aspects: Age Related Regular exercise reverses sarcopenia ¡ Aging of the cardiovascular system affects every organ in the body ¡ Atherosclerosis may block distal arteries, leading to intermittent claudication and causing severe pain in leg muscles ¡