Chapter 8 Muscle Physiology

Outline Structure Contractile mechanisms Mechanics Control Other muscle types Smooth, cardiac

Outline Structure Muscle fiber (from myoblasts) Myofibrils Thick and thin filaments (actin and myosin) A,H,M,I,Z Sarcomere Titin –elasticity Cross bridges Myosin, Actin, tropomyosin, troponin

Muscle Comprises largest group of tissues in body Three types of muscle Skeletal muscle Make up muscular system Cardiac muscle Found only in the heart Smooth muscle Appears throughout the body systems as components of hollow organs and tubes Classified in two different ways Striated or unstriated Voluntary or involuntary

Categorization of Muscle

Muscle Controlled muscle contraction allows Purposeful movement of the whole body or parts of the body Manipulation of external objects Propulsion of contents through various hollow internal organs Emptying of contents of certain organs to external environment

Structure of Skeletal Muscle Muscle consists a number of muscle fibers lying parallel to one another and held together by connective tissue Single skeletal muscle cell is known as a muscle fiber Multinucleated Large, elongated, and cylindrically shaped Fibers usually extend entire length of muscle

Muscle Tendon Muscle fiber (a single muscle cell) Connective tissue Fig. 8-2, p. 255

Structure of Skeletal Muscle Myofibrils Contractile elements of muscle fiber Regular arrangement of thick and thin filaments Thick filaments – myosin (protein) Thin filaments – actin (protein) Viewed microscopically myofibril displays alternating dark (the A bands) and light bands (the I bands) giving appearance of striations

Muscle fiber Dark A band Light I band Myofibril Fig. 8-2, p. 255

Structure of Skeletal Muscle Sarcomere Functional unit of skeletal muscle Found between two Z lines (connects thin filaments of two adjoining sarcomeres) Regions of sarcomere A band Made up of thick filaments along with portions of thin filaments that overlap on both ends of thick filaments H zone Lighter area within middle of A band where thin filaments do not reach M line Extends vertically down middle of A band within center of H zone I band Consists of remaining portion of thin filaments that do not project into A band

Z line A band I band Portion of myofibril M line H zone Sarcomere Thick filament A band I band Thin filament Cross bridges M line H zone Z line Myosin Actin Thick filament Thin filament Fig. 8-2, p. 255

I band A band I band Cross bridge Thick filament Thin filament Fig. 8-4, p. 256

Structure of Skeletal Muscle Titin Giant, highly elastic protein Largest protein in body Extends in both directions from M line along length of thick filament to Z lines at opposite ends of sarcomere Two important roles: Along with M-line proteins helps stabilize position of thick filaments in relation to thin filaments Greatly augments muscle’s elasticity by acting like a spring

Myosin Component of thick filament Protein molecule consisting of two identical subunits shaped somewhat like a golf club Tail ends are intertwined around each other Globular heads project out at one end Tails oriented toward center of filament and globular heads protrude outward at regular intervals Heads form cross bridges between thick and thin filaments Cross bridge has two important sites critical to contractile process An actin-binding site A myosin ATPase (ATP-splitting) site

Structure and Arrangement of Myosin Molecules Within Thick Filament

Actin Primary structural component of thin filaments Spherical in shape Thin filament also has two other proteins Tropomyosin and troponin Each actin molecule has special binding site for attachment with myosin cross bridge Binding results in contraction of muscle fiber

Composition of a Thin Filament

Actin and myosin are often called contractile proteins Actin and myosin are often called contractile proteins. Neither actually contracts. Actin and myosin are not unique to muscle cells, but are more abundant and more highly organized in muscle cells.

Tropomyosin and Troponin Often called regulatory proteins Tropomyosin Thread-like molecules that lie end to end alongside groove of actin spiral In this position, covers actin sites blocking interaction that leads to muscle contraction Troponin Made of three polypeptide units One binds to tropomyosin One binds to actin One can bind with Ca2+

Tropomyosin and Troponin When not bound to Ca2+, troponin stabilizes tropomyosin in blocking position over actin’s cross-bridge binding sites When Ca2+ binds to troponin, tropomyosin moves away from blocking position With tropomyosin out of way, actin and myosin bind, interact at cross-bridges Muscle contraction results

Role of Calcium in Cross-Bridge Formation

Cross-bridge interaction between actin and myosin brings about muscle contraction by means of the sliding filament mechanism.

Outline Contractile mechanisms Sliding filament mechanism (Theory) Ca dependence Power stroke T tubules Ca release Lateral sacs, foot proteins, ryanodine receptors, dihydropyradine receptors Cross bridge cycling Rigor mortis, relaxation, latent period

Sliding Filament Mechanism Increase in Ca2+ starts filament sliding Decrease in Ca2+ turns off sliding process Thin filaments on each side of sarcomere slide inward over stationary thick filaments toward center of A band during contraction As thin filaments slide inward, they pull Z lines closer together Sarcomere shortens

Basic 4 steps Fig. 8-9, p. 260 Figure 8.9: Cross-bridge activity. (a) During each cross-bridge cycle, the cross bridge binds with an actin molecule, bends to pull the thin filament inward during the power stroke, then detaches and returns to its resting conformation, ready to repeat the cycle. (b) The power strokes of all cross bridges extending from a thick filament are directed toward the center of the thick filament. (c) Each thick filament is surrounded on each end by six thin filaments, all of which are pulled inward simultaneously through cross-bridge cycling during muscle contraction. Fig. 8-9, p. 260

Hydrolysis of ATP pivots head Release of ADP and Pi cocks head Detailed steps Hydrolysis of ATP pivots head Release of ADP and Pi cocks head Figure 8.13: Cross-bridge cycle. Fig. 8-13, p. 263

Calcium Release in Excitation-Contraction Coupling

Power Stroke Activated cross bridge bends toward center of thick filament, “rowing” in thin filament to which it is attached Sarcoplasmic reticulum releases Ca2+ into sarcoplasm Myosin heads bind to actin Myosin heads swivel toward center of sarcomere (power stroke) ATP binds to myosin head and detaches it from actin

Power Stroke Hydrolysis of ATP transfers energy to myosin head and reorients it Contraction continues if ATP is available and Ca2+ level in sarcoplasm is high

Sliding Filament Mechanism All sarcomeres throughout muscle fiber’s length shorten simultaneously Contraction is accomplished by thin filaments from opposite sides of each sarcomere sliding closer together between thick filaments

Changes in Banding Pattern During Shortening

Relaxation Depends on reuptake of Ca2+ into sarcoplasmic reticulum (SR) Acetylcholinesterase breaks down ACh at neuromuscular junction Muscle fiber action potential stops When local action potential is no longer present, Ca2+ moves back into sarcoplasmic reticulum

Terminal button T tubule Acetylcholine- gated cation channel Lateral Surface membrane of muscle cell Acetylcholine- gated cation channel Lateral sacs of sarcoplasmic reticulum Acetylcholine Troponin Tropomyosin Actin Cross-bridge binding Myosin cross bridge Fig. 8-12, p. 262

T Tubules and Sarcoplasmic Reticulum

Sarcoplasmic Reticulum Modified endoplasmic reticulum Consists of fine network of interconnected compartments that surround each myofibril Not continuous but encircles myofibril throughout its length Segments are wrapped around each A band and each I band Ends of segments expand to form saclike regions – lateral sacs (terminal cisternae)

Transverse Tubules T tubules Run perpendicularly from surface of muscle cell membrane into central portions of the muscle fiber Since membrane is continuous with surface membrane – action potential on surface membrane also spreads down into T-tubule Spread of action potential down a T tubule triggers release of Ca2+ from sarcoplasmic reticulum into cytosol

Relationship Between T Tubule and Adjacent Lateral Sacs of Sarcoplasmic Reticulum

Outline Mechanics Tendons Twitch Motor unit Motor unit recruitment Fatigue Asynchronous recruitment Twitch, tetanus, summation Muscle length, isometric, isotonic Tension, origin, insertion

Skeletal Muscle Mechanics Muscle consists of groups of muscle fibers bundled together and attached to bones Connective tissue covering muscle divides muscle internally into bundles Connective tissue extends beyond ends of muscle to form tendons Tendons attach muscle to bone

Muscle Contractions Contractions of whole muscle can be of varying strength Twitch Brief, weak contraction Produced from single action potential Too short and too weak to be useful Normally does not take place in body Two primary factors which can be adjusted to accomplish gradation of whole-muscle tension Number of muscle fibers contracting within a muscle Tension developed by each contracting fiber

Motor Unit Recruitment One motor neuron and the muscle fibers it innervates Number of muscle fibers varies among different motor units Number of muscle fibers per motor unit and number of motor units per muscle vary widely Muscles that produce precise, delicate movements contain fewer fibers per motor unit Muscles performing powerful, coarsely controlled movement have larger number of fibers per motor unit

Motor Unit Recruitment Asynchronous recruitment of motor units helps delay or prevent fatigue Factors influencing extent to which tension can be developed Frequency of stimulation Length of fiber at onset of contraction Extent of fatigue Thickness of fiber

Schematic Representation of Motor Units in Skeletal Muscle

Twitch Summation and Tetanus Results from sustained elevation of cytosolic calcium Tetanus Occurs if muscle fiber is stimulated so rapidly that it does not have a chance to relax between stimuli Contraction is usually three to four times stronger than a single twitch

Summation and Tetanus

Muscle Tension Tension is produced internally within sarcomeres Tension must be transmitted to bone by means of connective tissue and tendons before bone can be moved (series-elastic component) Muscle typically attached to at least two different bones across a joint Origin End of muscle attached to more stationary part of skeleton Insertion End of muscle attached to skeletal part that moves

Fig. 8-17, p. 268 Figure 8.17: Length–tension relationship. Maximal tetanic contraction can be achieved when a muscle fiber is at its optimal length (lo) before the onset of contraction, because this is the point of optimal overlap of thick-filament cross bridges and thin-filament cross-bridge binding sites (point A). The percentage of maximal tetanic contraction that can be achieved decreases when the muscle fiber is longer or shorter than lo before contraction. When it is longer, fewer thin-filament binding sites are accessible for binding with thick-filament cross bridges, because the thin filaments are pulled out from between the thick filaments (points B and C). When the fiber is shorter, fewer thin-filament binding sites are exposed to thick-filament cross bridges because the thin filaments overlap (point D). Also, further shortening and tension development are impeded as the thick filaments become forced against the Z lines (point D). In the body, the resting muscle length is at lo. Furthermore, because of restrictions imposed by skeletal attachments, muscles cannot vary beyond 30% of their lo in either direction (the range screened in light green). At the outer limits of this range, muscles still can achieve about 50% of their maximal tetanic contraction. Fig. 8-17, p. 268

Types of Contraction Two primary types Isotonic Isometric Muscle tension remains constant as muscle changes length Isometric Muscle is prevented from shortening Tension develops at constant muscle length

Contraction-Relaxation Steps Requiring ATP Splitting of ATP by myosin ATPase provides energy for power stroke of cross bridge Binding of fresh molecule of ATP to myosin lets bridge detach from actin filament at end of power stroke so cycle can be repeated Active transport of Ca2+ back into sarcoplasmic reticulum during relaxation depends on energy derived from breakdown of ATP

Energy Sources for Contraction Transfer of high-energy phosphate from creatine phosphate to ADP First energy storehouse tapped at onset of contractile activity Oxidative phosphorylation (citric acid cycle and electron transport system Takes place within muscle mitochondria if sufficient O2 is present Glycolysis Supports anaerobic or high-intensity exercise

Muscle Fatigue Occurs when exercising muscle can no longer respond to stimulation with same degree of contractile activity Defense mechanism that protects muscle from reaching point at which it can no longer produce ATP Underlying causes of muscle fatigue are unclear

Central Fatigue Occurs when CNS no longer adequately activates motor neurons supplying working muscles Often psychologically based Mechanisms involved in central fatigue are poorly understood

Outline Other types Fibers Smooth, cardiac Creatine phosphate Fast slow Oxidative glycolytic Smooth, cardiac Creatine phosphate Oxidative phosphorulation Aerobic, myoglobin Glycolysis Anaerobic, lactic acid

Major Types of Muscle Fibers Classified based on differences in ATP hydrolysis and synthesis Three major types Slow-oxidative (type I) fibers Fast-oxidative (type IIa) fibers Fast-glycolytic (type IIx) fibers

Characteristics of Skeletal Muscle Fibers

Control of Motor Movement Three levels of input control motor-neuron output Input from afferent neurons Input from primary motor cortex Input from brain stem

Muscle Spindle Structure Consist of collections of specialized muscle fibers known as intrafusal fibers Lie within spindle-shaped connective tissue capsules parallel to extrafusal fibers Each spindle has its own private efferent and afferent nerve supply Play key role in stretch reflex

Muscle Spindle Function

Contractile end portions of intrafusal fiber Capsule Alpha motor neuron axon Intrafusal (spindle) muscle fibers Gamma motor neuron axon Contractile end portions of intrafusal fiber Noncontractile central portion of intrafusal fiber Secondary (flower-spray) endings of afferent fibers Primary (annulospiral) endings of afferent fibers Extrafusal (“ordinary”) muscle fibers Fig. 8-24, p. 283

Stretch Reflex Primary purpose is to resist tendency for passive stretch of extensor muscles by gravitational forces when person is standing upright Classic example is patellar tendon, or knee-jerk reflex

Patellar Tendon Reflex

Outline Other muscle types Smooth, cardiac This information is covered in detail in the lecture on the heart.

Smooth Muscle Found in walls of hollow organs and tubes No striations Filaments do not form myofibrils Not arranged in sarcomere pattern found in skeletal muscle Spindle-shaped cells with single nucleus Cells usually arranged in sheets within muscle Have dense bodies containing same protein found in Z lines

Smooth Muscle Cell has three types of filaments Thick myosin filaments Longer than those in skeletal muscle Thin actin filaments Contain tropomyosin but lack troponin Filaments of intermediate size Do not directly participate in contraction Form part of cytoskeletal framework that supports cell shape

Intermediate filament Thick filament Thin filament Dense body Stepped art Fig. 8-28, p. 288

Calcium Activation of Myosin Cross Bridge in Smooth Muscle

Comparison of Role of Calcium In Bringing About Contraction in Smooth Muscle and Skeletal Muscle

Smooth Muscle Two major types Multiunit smooth muscle Single-unit smooth muscle

Multiunit Smooth Muscle Neurogenic Consists of discrete units that function independently of one another Units must be separately stimulated by nerves to contract Found In walls of large blood vessels In large airways to lungs In muscle of eye that adjusts lens for near or far vision In iris of eye At base of hair follicles

Single-unit Smooth Muscle Self-excitable (does not require nervous stimulation for contraction) Also called visceral smooth muscle Fibers become excited and contract as single unit Cells electrically linked by gap junctions Can also be described as a functional syncytium Contraction is slow and energy-efficient Well suited for forming walls of distensible, hollow organs

Cardiac Muscle Found only in walls of heart Striated Cells are interconnected by gap junctions Fibers are joined in branching network Innervated by autonomic nervous system