Muscle

I.                 Three human muscle types

A.     Skeletal

§  Striated, usually voluntary contraction (diaphragm involuntary)

§  Larger fiber, peripheral nuclei

B.     Cardiac

§  Striated, involuntary

§  Smaller fiber, central nuclei

C.    Smooth

§  Non-striated, involuntary

§  Central nuclei

II.               Skeletal muscle

A.     Macrostructure

§  Muscle fiber- each fiber is an elongate, multi-nucleate cell from fusion of myoblast in embryo

§  Each fiber is surrounded by endomysium

§  Muscle fasicicle- group of fibers surrounded perimysium (thicker protective sheath)

§  Bundle of fascicles surrounded by CT called epimysium

§  Can be grouped as broad sheets (rectus abominis), bundles (biceps), or circular arrays (obsicularis oris, anal, urinary sphincters)

§  Contract in parallel with orientation of fibers

§  Pink-red color of muscle due to blood supply and myoglobin

§  Contractile force transmitted to boneor other muscle by myotendonal junctions, then connective tendons

§  Diaphragm contraction is involuntary (sleep)

§  Three fiber types:  fast twitch, glycolytic FG;  slow twitch, oxidative SO; fast twitch, oxidativeglycolytic FOG;  fast/ slow innervation determines fiber type

FG, fast glycolytic

SO, slow oxidative

Color

white

Red

Contraction

fast

Slow

Metabolism

Glycolytic (anaerobci)

Oxidative (aerobic)

Substrate

Glucose

Fatty acid

Endurance

low

High

Blood supply

low

High

Fiber diameter

Large

Small

Mitochondria

few

Many

Lipid droplets

few

Many

Sarcoplasmic reticulum

extensive

Sparse

Myoglobin

low

High

Glycogen

high

Low

Myosin ATPase

high

Low

B.     Cellular Structure

§  Overall regular striated appearance due to myofibrils in each cell or fiber (bundle of spaghetti)

§  Contractile elements are repeating sarcomeres

Sarcomeres composed of following:

§  Z-line:

at end of sarcomere

contains actinin (actin binding proteins)

Zwischenscheibe (between band)

bisects I band

§  I-band:

actin thin filaments

tropomyosin and troponin (regulatory proteins)

isotropic (does not bend light)

width decreases with contraction

§  A-band:

Myosin and actin

Anisotropic (bends light), shows up dark (part over lap with actin), gives striated appearance

Width remains constant with contraction

§  H-band

Myosin thick only

Central regionof A bnd

Heller,light

Width decreases with contraction

§  M-line

Middle of H-band

Myosin joined laterally to its neighbor

“mittel” line = middle line

Four major proteins comprising myofibrils

§  Myosin

Major component of thick filaments

Golf club with two heads

Head contains ATPase and light chain proteins (regulate interaction with actin)

§  Actin

Major component of thin filaments

Globular G- actin link end to end to form filamentous (F-actin)

Actin strands entwine to form thin filament

§  Tropomysosin

Long protein molecule that lies in groove of two actin strands

§  Troponin (three subunits)

TnT- binds to troposyosin

TnC- binds Ca++

TnI- inhibits actin-myosin interaction

One troponin complex binds to one tropomyosin molecule, spans 7 G-actin

Membrane systems

§  Sarcolemma (SL)

Plasma membrane of muscle cell- ion transport proteins, ion channels, receptors to regulatge ion flow and metabolism

Invaginated in striated muscles (cardiac: one at each Z-band ,  skeletal: one on either side of Z-line= form T-tubule)

Brins depolarization signal deep in muscle cell

Specialized region in SKELETAL muscle fiber form post synaptic membrane of motor end plate

§  Sarcoplasmic reticulumn (SR)

Internal membrane network

Noconnection with extgracillular apce

Junctional complexes with T-tubules (skeletal-triad, cardiac-dyad)

Takes up and releases Ca++ to regulate contraction

§  Mitochondria

Elongate and branch through and around myofibrils

Product ATP for contraction and membrane ion pumps

Smaller under sarcolemma and around nuclei

§  Nucleus

Many, almost end to end beneath sarcolemma

§  Others

Glycogen particles, golgi, lysosomes, peroxisomes

C.    Contractile event

§  Each muscle fiber is innervated by one motor neuron via motor end plate (neuromuscular juction)

§  ACH stored n synaptic vesicles

§  Impulses produces fusion of vesicles with nerve presynaptic membrane and ACH discharged in synaptic cleft

§  ACH bidns to receptor on muscle postsynaptic membrane resulting in Na+ influx and depolarization

§  Depolarization spreads outward over SL and down T-tubules

§  At triad, depolarization sensed by SR via dense feet

§  Stored Ca++ in SR released into sarcoplasm

§  Sarcoplasmic [Ca++] increases from 10-7 to 10-5

§  Ca++ binds to TnC causeing conformational change

§  Tn change alters tropomyosin to uncover actin

§  Myosin head-ATP interacts with actin

§  Myosin head activated, hydrolyses ATP

§  Ratcheting of attached myosin head pulls actin into A band

§  Z-Z distance decreases as sarcomere shortens, I band decreases, A band constant

§  Cyclic repeats of myosin-ATP formation, ATP hydrolysis, and contraction until full contraction of sarcomeres

§  Uptake of Ca++ by SR

§  Muscle relaxes

III.              Cardiac muscle

A.     Macrosturcture

§  Individual cells joined by intercalated disks (specialized electro-mechanical junctions)

§  Branching fibers

§  Connective tissue interspersed, nofascicular structure

§  No direct innervation

§  Dense vascularization

B.     Cellular Organization

§  Striated appearance, 1-2 centrally placed nuclei

§  Considerable branching

§  T-tubulues larger diamer and occur at Z-band

§  SR tubule juctionis dyad

§  SR less extensive

§  High mitochondrial density

§  Intercalated disks connect cardiac muscle cells at membranes

Three types of membrane specialization

§  Macula adherens (desmosomes)- perpenduclar to region of intercalated disks

§  Fascia adherens- ends of filaments anchor into felt like mat on membrane; perpendicular orientation

§  Gap junction (nexus)- low resistance electrical coupling b/t two cardiac muscles

IV.             Smooth muscle

A.     Macrostructure

§  Can be bundles or shetts, longitudinally or circular

§  Paler than cardiac or SO skeletal due to lower vacularization and low myoglobin content

§  Endomysium is sparse

§  Spindle shaped cells, nucleus has staggered appearance

B.     Cellular Organization

§  Spindle shaped cells

§  Nostrations or sarcomeres

§  Action and myosin bundles anchor on SL membrane dense bodies, organization is diagonal

§  SR not as distinct

§  No T-tubules

§  Cgapjuctions between cels

§  Autonomic nerve endings

V.               Cellular control and innervation

A.     Skeletal

§  Each fiber receives electrical stimulation via branch of motor neuron

§  Each motor neuron may innervate up to 100 muscle fibers

§  Combination of neuron and muscle fibers termed the motor unit

§  Stimulation of motor nerve results in contraction in an all or none response

§  Strength, speed, and duration à type of sk.muscle, number of motor units stim, frequency of stim

§  Connection between nerve and muscle is termed the motor end plate (neuromuscular junction)

§  Motor axon terminal contains ACH, fuse into pre-synaptic membrane of motor end plate

§  Release AH into synaptic cleft and activate receptor on post synaptic membrane

§  Influx of Na+ initiates contractile response by elevation of sarcoplasmic Ca++

§  Proprioreceptors as well as tendons, joints provide feedback on muscle contractile state and tendon tension and position of joint

§  Muscle spindle found in skeletal muscles- 2-20 intrafusal muscle fibers, an afferent nerve ending enclosedin a connective tissue capsule

§  Stretch muscle, stretch spindle, stimulates nerve ending, AP sense by sp.ch., motor neuron stimulated, muscles contracts

§  Golgi tendon organ is sensory nerve ending in tendon which inhibits muscle contraction when it senses excess tension placed on tendon by muscle.

§  Several types of joint receptors, sense joint positions

B.     Cardiac

§  Contraction without direct nerve stimulation

§  Initiating wave of depolarization orginates at SA node, travels thru conductive pathway (AV, bhundle of his, purkinje fibers)

§  Nodal conductive pathway cells are shorter and paler staining

§  Heart rate affected by autonomic innervation of Sa node and other reigions by vagus nerve, also hormones

§  Contractile activities dependent on neighboring cell depolarizations

C.    Smooth

§  Regulated by autonomic innervation and resonds to hormones

§  Contractile activating depolarization passes from cell to cell like cardiac muscle via gap junctions

§  Contraction slow (wave like)

§  Depolarization of SL causes increaseof sarcoplasmic Ca++

§  Actin-myosin interaction mediated through calmodulin

§  Calmodulin activates myosin light chain kinase, which phosphorylate myosin light chain permitting myosin to interact with actin

§  No troponin regulation

§  Cells becomeshortrand fatter in contraction

VI.             Development, adaptation, regeneration

A.     Skeletal

§  Fusion of myoblast form multinucleate cell myotube syncytia which synthesize contractile proteins to become mature fibers

§  Once fiber is formed, no further division

§  Can hypertrophy (enlarge) in response to exercise  or hormones

§  Atrophy in response to inactivity, injury, oss ofinnervation or malnutrition

B.     Cardiac

§  Myocardium develops from splanchnic mesodermal cells

§  Once formed no further division

§  No satellite cells, tissue has no capacity for replacement of damaged cells

§  CT replaces dead myocardial cessl

§  Hypertrophy in response to increase vascular resistance or exercise

§  Atrophy in response to decreased workload

C.    Smooth

§  Hypertrophy in response to increased demand

§  Hyperplasia (increase number of cells) by division

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