MUSCLE W Beresford MUSCLE CONTRACTION: Requirements MUSCLE CONTRACTION:

MUSCLE W Beresford MUSCLE CONTRACTION: Requirements MUSCLE CONTRACTION: Requirements THREE MAIN TYPES OF MUSCLE MUSCLE CONTRACTION: Requirements SKELETAL MUSCLE THREE MAIN TYPES OF MUSCLE: Sub-types SKELETAL MUSCLE: Connective Tissue Organization PERIPHERAL MYOFIBRIL IN LONGITUDINAL EM VIEW BANDING-PATTERN CHANGES IN CONTRACTION SKELETAL MYOFIBER: Needs determining structure

SKELETAL MYOFIBER: Initiating contraction SKELETAL MYOFIBER: Generating contraction Details of actin-myosin interaction to generate myosins pull on actin filament MYOFIBER: Stabilization* & Force Application materials SKELETAL MUSCLE: INNERVATION MOTOR END-PLATE or NEUROMUSCULAR/MONEURAL JUNCTION MOTOR END-PLATE: LOCATION OF TRANSMISSION MOLECULES SMOOTH MUSCLE CARDIAC MUSCLE INTERCALATED DISC - electro-mechanical union PURKINJE FIBER MUSCLE CELLS ROLE Muscle cell contracts along an axis to furnish force

applied to what it is attached to MUSCLE CELL = MUSCLE FIBER Muscle cells are often called muscle fibers. Note the distinction with connective tissue cells, which construct extracellular fibers such as collagen. Muscle cells are also called myocytes, e.g., cardiomyocyte MUSCLE ACTIONS Muscle cells work together as muscles (abs. etc) or layers of heart or tubes, for a purpose Visceral Somatic skeletal

muscle rotation around joint* squeezing/ * constriction * how the force is applied lumen MUSCLE CONTRACTION: Requirements Generated Applied usefully Controlled Energized Sustained Varied for conditions

MUSCLE CONTRACTION: Requirements GENERATED by interactions between actin & myosin Applied usefully connective tissues to tendons; visceral & cardiac muscle contract in a circle CONTROLLED voluntary & involuntary: nervous; & nervous + diffuse chemical control ENERGIZED blood supply; mitochondria ; ATP; glycogen - stored form of glucose SUSTAINED multiple muscle units; prolonged contraction (smooth muscle) VARIED FOR CONDITIONS sub-types of muscle The diverse requirements demand 3 three separate kinds of muscle THREE MAIN TYPES OF MUSCLE

SMOOTH small but prolongable force; diverse types, uses, & controls; controlled partly by autonomic/involuntary nervous system, partly by chemicals released from nearby cells, and by cell-to-cell connections CARDIAC strong rhythmic contractions; controlled by own cell-to-cell connections; pace determined by autonomic innervation to a little of the cardiac muscle SKELETAL most forceful kind, but contracts only in response to voluntary/somatic nervous system activity; applies its force via well-organized connective tissue; strength of contraction needs high internal organization within the muscle cell/fiber THREE MAIN TYPES OF MUSCLE III SKELETAL most forceful kind; but contracts only in response to

voluntary/somatic nervous system activity; applies its force via well-organized connective tissue; strength of contraction needs high internal organization within the muscle cell/fiber MUSCLE CONTRACTION: Requirements Applied usefully connective tissues to tendons; SKELETAL MUSCLE striated/cross-banded myofiber sarcolemma

capillary TENDON multi-nucleated, peripheral nuclei satellite cell Myofiber in cross-section endomysium CT myofibrils SKELETAL MUSCLE: Connective Tissue Organization

MYOCYTE PERIMYSIUM } creates FASCICLE/ bundle endomysium EPIMYSIUM MUSCLE CONTRACTION: Requirements GENERATED by interactions between actin & myosin

Myofiber in cross-section myofibrils Each myofibril consists of bundled myofilaments thick MYOSIN thin ACTIN But, at regular intervals along the relaxed fiber, only thin or only thick filaments are found. Why? ACTIN & MYOSIN FILAMENTS IN MUSCLE Z line/disc

thin ACTIN filament thick MYOSIN filament In muscle, for strong shortening (contractile) force the actin filaments are stabilized and interdigitated with thicker myosin filaments, which pull them in deeper PERIPHERAL MYOFIBRIL IN LONGITUDINAL EM VIEW I band Z line/disc thin ACTIN filament A band I band

H zone with M line thick MYOSIN filament Banding pattern - I & A bands, Z lines, H zones, M lines PERIPHERAL MYOFIBRIL IN LONGITUDINAL EM VIEW I band A band I band Z line/disc thin ACTIN filament thick MYOSIN filament

Cross-section hits thick & thin Hits only thin BANDING-PATTERN CHANGES IN CONTRACTION A band I band Z line 1 I band

M line but no myosin H zone Sarcomere shortens 3 A band unchanged 2 I band shortens 4 H zone disappears actin SKELETAL MYOFIBER: Needs determining structure

Generation Force generation Stabilization Force application Control of contraction Energize SKELETAL MYOFIBER: Initiating contraction T/transverse tubule A-I junction Z line motor end-plate

sarcolemma Sarcoplasmic reticulum wraps around myofibril Feet and releases Calcium ion, when stimulated via Terminal cisterna of T-tubule & feet SR } Triad = Ttubule + two terminal cisternae

Motor end-plate - Sarcolemma AP - T-tubule AP - Feet - SR - Ca 2+ release AROUND EACH MYOFIBRIL, meaning between myofibrils Glycogen granules energize Sarcoplasmic reticulum control Myofilaments generate force Mitochondria energize

MYOFIBRIL SKELETAL MUSCLE: MOTOR INNERVATION Axons/nerve fibers to motor end-plates to cause contraction striated/cross-banded myofiber Wide extrafusal muscle fibers TENDON Muscle spindle Thin intrafusal muscle fiber MOTOR END-PLATE or NEUROMUSCULAR/MYONEURAL JUNCTION AXON SCHWANN

CELL AXOLEMMA SARCOLEMMA SYNAPTIC VESICLES mitochondrion synaptic cleft secondary/ junctional folds of POST-SYNAPTIC MEMBRANE SKELETAL MUSCLE FIBER/MYOCYTE

MOTOR END-PLATE: LOCATION OF TRANSMISSION MOLECULES SARCOLEMMA voltage-gated ion channels AXOLEMMA voltage-gated ion channels Acetyl Choline/ACh SYNAPTIC VESICLES synaptic cleft Cholinesterase PRE-SYNAPTIC

MEMBRANE Ca2+ channels Ligand-gated ion channels ACh receptors POST-SYNAPTIC MEMBRANE SKELETAL MUSCLE FIBER/MYOCYTE THREE MAIN TYPES OF MUSCLE II CARDIAC strong rhythmic contractions; controlled by own cell-to-cell connections; pace determined by autonomic innervation to a little of the cardiac

muscle striated, but less conspicuously than skeletal m. CARDIAC MYOCYTE IN LONGITUDINAL EM VIEW I band A band I band H zone with M line Sometimes an thick MYOSIN filament thin ACTIN filament intercalated disk Banding pattern - I & A bands, Z lines, H zones, M lines

Z line/disc The regular arrangement of the filaments & their attachments yields a visible banding pattern across the fiber CARDIAC MUSCLE striated/cross-banded CARDIOMYOCYTES INTERCALATED DISK Reticular fiber Capillary central NUCLEUS

branching muscle fibers Sarcolemma & external lamina INTERCALATED DISC - electro-mechanical union ID is a strong myocyte-myocyte attachment + electrical connections Fascia adherens strength Maculae adherens strength Gap junction transmits contraction HEARTS CONDUCTION SYSTEM Connective tissue separating atria from ventricles

SINU-ATRIAL NODE Left ATRIUM BUNDLE OF HIS ATRIAL MUSCLE ATRIAL MUSCLE Right ATRIUM ATRIOVENTRICULAR NODE

LEFT BUNDLE Left VENTRICLE Right VENTRICLE VENTRICULAR MUSCLE Interventricular septum HEARTS CONDUCTION SYSTEM: Purkinje fibers Left ATRIUM BUNDLE OF HIS LEFT BUNDLE Right ATRIUM

PURKINJE FIBERS, also found in Bundles Left VENTRICLE Right VENTRICLE VENTRICULAR MUSCLE RIGHT BUNDLE PURKINJE FIBERS are modified, highly excitable, fast conducting, well connected muscle fibers to coordinate ventricular contractions PURKINJE FIBER ventricle

} Endocardium Subendocardium Large, pale cell specialized for conduction, not contraction Myofilaments Glycogen VESSELS - Lab Problems 3* Arterial valve Connective tissue of cardiac skeleton Elastic artery Myocardium Pericardial adipose tissue

Endocardium THREE MAIN TYPES OF MUSCLE I SMOOTH small, but prolongable force; diverse types, uses, & controls; controlled partly by autonomic/ involuntary nervous system, partly by chemicals released from nearby cells, and by cell-to-cell connections SMOOTH MUSCLE SMOOTH MUSCLE CELL has same contractile & control

*machinery as skeletal myocyte, but less organized Reticular fiber Autonomic nerve axon Gap junction/Nexus Myocyte plasmalemma + glycoprotein External lamina * There is the important difference that smooth muscle uses Myosin Lightchain Kinase (MLCK) to phosphorylate the regulatory myson light chain as the main means to provoke the actomyosin ATPase to start contraction SMOOTH MUSCLE SMOOTH MUSCLE CELL has same contractile & control machinery as skeletal myocyte, but less organized

Filaments attach to DENSE BODIES serving the role of Z-lines CAVEOLAE for stimuluscontraction coupling serve role of T-tubule & SR system CAVEOLA Caveolae are plasma membrane invaginations found in most cell types of all four tissues. They are conspicuous in endothelial cells & smooth muscle. Membrane molecules: Caveolin - characteristic integral membrane protein Plasmalemma

Cholesterol (lots) Molecules related to Transcytosis Endocytosis or Signal transduction SMOOTH MUSCLE * There is the important difference that smooth muscle uses Myosin Light-chain Kinase (MLCK) to phosphorylate the regulatory myosin light chain as the main means to provoke the actomyosin ATPase to start contraction SMOOTH MUSCLE View with H & E staining - solid pink mass (stained sarcoplasm)

crosssection long.section Unseen are reticular and nerve fibers, plasmalemmas & external laminae Trichrome stains distinguish smooth muscle cells from collagen fibers Just put your finger here, and see who was first with cutting edge. MUSCLE CONTRACTION: Requirements GENERATED by interactions between actin & myosin Applied usefully connective tissues to tendons; visceral & cardiac muscle contract in a circle

CONTROLLED voluntary & involuntary: nervous; & nervous + diffuse chemical control ENERGIZED blood supply; mitochondria ; ATP; glycogen - stored form of glucose SUSTAINED multiple muscle units; prolonged contraction (smooth muscle) VARIED FOR CONDITIONS sub-types of muscle The diverse requirements demand 3 three separate kinds of muscle SKELETAL MYOFIBER: Needs determining structure Generation Force generation Stabilization

Force application Control of contraction Energize SKELETAL MYOFIBER IN LONGITUDINAL EM VIEW I band Z line/disc thin ACTIN filament A band I band H zone with M line thick MYOSIN filament

Banding pattern - I & A bands, Z lines, H zones, M lines SKELETAL MYOFIBER: Generating contraction Z line/disc thin ACTIN filament ACTIN filament attached globular F actin molecules H zone with M line thick MYOSIN filament Tails of heavy (H) myosin bundle together to make the myosin filament H & L myosin heads hinge stepwise along actin filament

Actin-myosin interaction to generate myosins pull on actin filament Myosin head / Motor domain Parts of Motor domain Actin-binding site Regulatory domain interacts with tropomyosin under control of Ca 2+ --switched troponin Thick filament - Rods of H myosin Catalytic domain

Actin filament myosin rods held stationary 2 Actin filament ATP-catalysing site 1 Regulatory domain does the lever work, aided by the flexible start of the rod pulled

BANDING-PATTERN CHANGES IN CONTRACTION A band I band Z line 1 I band M line but no myosin H zone Sarcomere shortens

3 A band unchanged 2 I band shortens 4 H zone disappears actin MYOFIBER: Stabilization* & Force Application materials Sarcolemma a-actinin* Z line External lamina

Nebulin* Dystrophin Integrin M line* Titin* (elastic) Desmin* intermediate filaments SKELETAL MYOFIBER: Needs determining structure Generation

Force generation Stabilization Force application Control of contraction Energize SKELETAL MYOFIBER: Initiating contraction (RyanR) T/transverse tubule A-I junction motor end-plate sarcolemma

Z line Ryanodine receptor at Sarcoplasmic reticulum wraps around myofibril and releases Calcium Feet ion, when stimulated via Terminal cisterna of T-tubule & feet SR } Triad = Ttubule + two

terminal cisternae Motor end-plate - Sarcolemma AP - T-tubule AP - Feet - SR - Ca 2+ release SKELETAL MUSCLE: SENSORY INNERVATION striated/cross-banded myofiber TENDON Golgi tendon receptor Muscle spindle Sensory axon & spindle receptor The fine control of contraction in individual myofibers requires abundant sensory feedback on how the muscle as a whole is performing

SKELETAL MUSCLE: INNERVATION Axons/nerve fibers to motor end-plates to cause contraction striated/cross-banded myofiber TENDON Golgi tendon receptor Muscle spindle Sensory axon & spindle receptor The fine control of contraction in individual myofibers requires abundant sensory feedback on how the muscle as a whole is performing

SKELETAL MUSCLE: Satellite cells & Repair striated/cross-banded myofiber sarcolemma capillary TENDON multi-nucleated, peripheral nuclei satellite cell for repair endomysium CT

Satellite cellsscan become myoblasts to restore the muscle fiber after damage THREE MAIN TYPES OF MUSCLE: Sub-types SMOOTH skin, cardiovascular, airway, uterine, other reproductive eye urinary, gastrointestinal (GI) CARDIAC atrial, ventricular, nodal, Purkinje

SKELETAL oxidative, type I - slow, type IIa - fast type IIb - fast glycolytic ELASTIC ARTERY * { Intima Media { Adventitia {

Endothelium Smooth muscle cells Collagen Vasa vasorum Elastic laminae Vascular SMCs make much ECM: collagen fibers, elastic membranes, & other macromolecules CARDIAC MUSCLE INTERCALATED DISK striated/cross-banded CARDIOMYOCYTES

Reticular fiber Capillary central NUCLEUS Sarcolemma & external lamina branching muscle fibers ATRIAL HEART & ANF Reticular fiber Atrial myocytes have a well developed Golgi complex and

secretory granules Atrial Natriuretic Factor (ANF) in the granules STIMULATES: diuresis; sodium excretion (natriuresis); vasorelaxation; & INHIBITS the Renin-Angiotensin system & aldosterone secretion CARDIAC PATHOLOGY Enlarged, but altered and weakened muscle of Ventricular hypertrophy Reticular fiber More & thicker fibers of Fibrosis Capillary Bad gap junctions altered connexin

Blocked vessels Arrythmia* damaged heart muscle (Cardiac infarct) *Most Arrythmias arise from defective ion channels THREE MAIN TYPES OF MUSCLE: Sub-types SMOOTH skin, cardiovascular, airway, uterine, other reproductive, urinary, gastrointestinal (GI) CARDIAC atrial, ventricular,

nodal, Purkinje SKELETAL oxidative, type I - slow, type IIa - fast type IIb - fast glycolytic SUB-TYPES OF SKELETAL MUSCLE I The principal division youve met at the dinner table: dark- and white-meat parts of the birds musculature. Dark muscle is for prolonged use, requiring endurance, as in the postural muscles of the human back and legs holding one upright White muscle provides for faster, more varied uses, ranging from eye movements to piano playing Some muscles are purely of one fiber type, but most are

mixtures of fiber types. The types are: Type I - SLOW - slow oxidative versus Type II - FAST - glycolytic & variable oxidative potential This difference, based on speed of contraction, endurance, and metabolic profile, is only the start of the great diversity, & ability to change - plasticity SUB-TYPES OF SKELETAL MUSCLE II This is only the start of the diversity, expressed in all of these: Glycogen granules energize Sarcoplasmic reticulum control Troponinin & tropomyosin control

Myofilaments generate force Mitochondria energize MYOFIBRIL SUB-TYPES OF SKELETAL MUSCLE III Type I - SLOW - slow oxidative Many mitochondria Type II - FAST - glycolytic

Fewer mitochondria More oxidative-pathway enzymes e.g., succinic dehydrogenase Fewer glycogen granules Much glycogen More glycolyticpathway enzymes More myoglobin Less myoglobin SUB-TYPES OF SKELETAL MUSCLE IV Type I - SLOW - slow oxidative

Type II - FAST - glycolytic Many mitochondria Fewer glycogen granules Fewer mitochondria More oxidative-pathway enzymes More glycolytic-pathway enzymes More myoglobin Less myoglobin

Much glycogen e.g., succinic dehydrogenase Slow myosin chains energize Fast myosin chains Slow troponinin & tropomyosin isoforms Fast troponinin & tropomyosin isoforms Slow levels of Ca2+-related

proteins Fast levels of Ca2+-related proteins Slow receptors & innervation generate force & control Fast receptors & innervation SUB-TYPES OF SKELETAL MUSCLE V The types are: Type I - SLOW - slow oxidative versus Type II - FAST - glycolytic & variable oxidative potential

The differences are quantitative, and qualitative, in the expression of specific proteins, but more often as isoforms of general protein species (e.g., MHCs) There is so much variety, change with aging and disease, and variation from one mammal to another, that the classification schemes are multiple and complex The control of gene expression to establish, then maintain, the appropriate levels and kinds of the many metabolic, contractile and regulatory proteins is under intensive study, but is still poorly understood However, changes in fiber type with certain neuromuscular disease are detectable, and known well enough for clinical usefulness SUB-TYPES OF SKELETAL MUSCLE VI There is so much variety, change with aging and disease, and variation from one mammal to another that the classification

schemes are multiple and complex Adding an intermediate type does not suffice The control of gene expression to establish, then maintain, the appropriate levels and kinds of the many metabolic, contractile and regulatory proteins is under intensive study, but is still poorly understood The differences are both quantitative, and qualitative, in the expression of specific proteins, but more often as isoforms of general protein species (e.g., MHCs) For the real flavor of all this, try Chin ER et al. Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin. J Physiol 2002;547:649663. The article also discusses classifications and results for human eye muscles. See also Kjellgren D et al. Myosin heavy chain isoforms in human extraocular muscles. Invest Ophthalmol Vis Sci 2003;44:1419-1425