Muscle Physiology PDF - Sherwood, Ninth Edition

Chapter 8 Muscle Physiology Sherwood, Ninth Edition Dr Panayiotis Avraamides MBBS Lon, BSc, FRCP Lon, FRCP Edin, FESC, FEACVI, FACC, FAHA, FSCAI, FHRS Clinical Professor of Cardiology  Outlin e How is muscle contraction effected ? To und...

Chapter 8 Muscle Physiology Sherwood, Ninth Edition Dr Panayiotis Avraamides MBBS Lon, BSc, FRCP Lon, FRCP Edin, FESC, FEACVI, FACC, FAHA, FSCAI, FHRS Clinical Professor of Cardiology  Outlin e How is muscle contraction effected ? To understand, need to know about muscle Structure Contractile mechanisms Mechanics Control Muscle types – Skeletal, Smooth, Cardiac  Structure of Skeletal Muscle Muscle: Half of the body’s weight Skeletal muscle: 40% of the body weight (men) 32% (women) Smooth and cardiac muscles make up10% of the body weight Muscles categorized a. as striated (skeletal and cardiac muscle) (depending on alternating dark and light band) vs unstriated (smooth muscle) b. Voluntary (innervated by somatic nervous system) vs unvoluntary (innervated by autonomic nervous system)  Muscle fiber of skeletal muscle Single skeletal muscle cell=muscle fiber Large, elongated, cylinder-shaped Number of muscle fibers bundled together by connective tissue A skeletal muscle fiber contains numerous myofibrils (cylindrical and extend the entire length of the muscle fiber) Myofibril contains contractile elements (thick and thin filaments) Structure of Skeletal Muscle  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 Mnemonic: dArk = A band lIght = I band Muscle fiber Dark A band Light I band Muscle fibre (muscle cell) M y o f i bFig. 8-2, p. 255  Structure of Skeletal Muscle DArk Band (A Band)=set of thick filaments along with the portion of the thin filaments that overlap on both ends of the thick filaments LIght Band (I Band)=the remaining portion of the thin filaments that do not overlap with thick filaments H Zone=lighter area within the middle of the A (Dark) band (only thick filaments) M Line=supporting proteins that hold the thick filaments together vertically Z Line (or Z disc)=In the middle of each I band there is a dense vertical line  Z line A band I band Portion of myofibril M line H zone Sarcomere Thick filament A band I band Thin filament Cross M line H zone Z line bridges Myosin Actin Thick filament Thin filament Fig. 8-2, p. 255  I band A band I band Myofibri Cross bridge l Cross-bridges=extend from each filament toward the surrounding thin filaments Thick filament Thin filament Fig. 8-4, p. 256 Changes in Banding Pattern During Shortening  Structure of Skeletal TitinMuscle – 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 Skeletal Muscle Sarcomere = the contractile Functional Anatomy unit of a muscle fibre (cell) Sarcomere is composed of various microfilaments and supporting structures Titin – largest known elastomeric protein – Connects myosin to z-disc – thought to be critical in the development of sarcomeres  Myosi n 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  Acti Primary structural component of thin filaments n 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. Neither It is theactually contractsbetween them which relative movement causes shortening = contraction 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 Their role in covering (preventing contraction) or exposing (permitting contraction) the binding sites for cross-bridge interaction between actin and myosin 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+ Role of Calcium in Cross-Bridge Formation 4. 1. 2. 3.  Tropomyosin and Troponin Troponin – When not bound to Ca2+, troponin stabilizes tropomyosin in blocking position over actin’s binding sites – When Ca2+ binds to troponin, the shape of tropomyosin changes, tropomyosin moves away from blocking position – With tropomyosin out of way, actin and myosin bind, interact at cross-bridges – Muscle contraction results  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 T Tubules and Sarcoplasmic Reticulum T tubules (the surface membrane -sarcolema- dips into the muscle fiber to form a T(transverse) tubule)  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) Sarcoplasmic Reticulum (SR) Sarcoplasmic Reticulum surrounds muscle fibres  ensures fast, simultaneous spread of muscle action potential  simultaneous contraction  Cross-bridge interaction between actin and myosin brings about muscle contraction by means of the sliding filament mechanism Sliding Filament mechanism=the thin filaments slide inward over the stationary thick filament Neither the thick nor the thin filaments decrease in length to shorten the sarcomere Basic 4 steps Fig. 8-9, p. 260 Calcium Release in Excitation-Contraction Coupling Skeletal Muscle Physiology of Contraction Relationship Between T Tubule and Adjacent Lateral Sacs of Sarcoplasmic Reticulum  Relaxatio n Depends on reuptake of Ca into 2+ 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  Excitation-Contraction Coupling Summary of Muscle contraction Alpha motor neurons release Ach ACh produces large EPSP in muscle fibers (via nicotinic Ach receptors) EPSP evokes action potential Action potential (excitation) triggers Ca2+ release, leads to fibre contraction Relaxation: Ca2+ levels lowered by organelle reuptake into the  Smooth Muscle cells Smooth muscle cells Small (2-10 μm vs 50-400 μm), unstriated (called “smooth”) Are found in the walls of organs and tubes Their contraction exerts pressure Single nucleus Elongated, arranged in sheets  Smooth Muscle cells Filaments thick myosin filament, thin actin filament, contain tropomyosin (but not troponin) and filaments of intermediate size (cytoskeleton) Are not arranged as a sarcomere No Z-lines but dense bodies Thick and thin filaments are oriented slightly diagonally (diamond-shaped)  Smooth Muscle cells Smooth muscle cells are turned on by Ca+2-dependent phosphorylation of myosin Tropomyosin does not block actin’s cross-bridge binding sites Light chains=have critical regulatory function  Smooth Muscle cells Myosin can interact with actin only when the light chain is phosphorylated Increased cytosolic Ca2+ leads to phosphorylation of myosin light chain Ca2+ binds with Calmodulin (similar to troponin) Ca2 calmodulin complex binds and activates another protein myosin light chain kinase (MLC Kinase) leads to phosphorylation of the myosin light chain  Smooth Muscle cells Phasic smooth muscle : contracts in bursts triggered by AP that leads to increasing cytosolic Ca2+ Tonic smooth muscle: partially contracts at all times, relatively low resting potential (tonic contraction in small blood vessels), maintains tone  Smooth Muscle cells Has no T Tubules and a poorly developed SR In phasic smooth muscle the increased cytosolic Ca2+ comes from two sources: extracellular fluid and some released from the sparse SR In tonic smooth muscle an extracellular chemical messenger such as norepinephrine promotes increasing cytosolic Ca2+ and increases BP (vasoconstriction)  Smooth muscle cells Differences in terms of excitation Multiunit vs single unit Multiunit smooth muscle cell is neurogenic (nerve produce), multiple discrete units that function independently and must be separately stimulated by nerves (e.g. walls of large blood vessels, small airways of the lung)  Smooth muscle cells Single unit=forms functional syncytia (visceral smooth muscle), muscle fibers are electrically lined by gap junctions, self-excitable (either phasic or tonic)  Cardiac muscle Shares structural and functional features with both skeletal and single-unit muscle cell Striated, thick and thin filaments, with troponin and tropomyosin, lots of mitochondria and myoglobin, T-tubules and moderately well- developed SR Cardiac Muscle fibers: slender and short (10-20μm in diameter and 50-100μm long) Pacemaker activity (without external influence) Cardiac cells are interconnected by gap junctions (found in intercalated discs) THANK YOU FOR YOUR ATTENTION !