1. Muscle Tissue Function Essentials Ch 16 p 536-542

2. The Contractile Unit  Sarcomere  Runs from Z-line to Z-line  Unit includes a number of specific and highly organized groups of proteins  Each group of proteins fulfills a specific function within the unit

3. Protein Components of Muscle Contraction  Thin filaments or Microfilaments l Globular Actin - G-Actin l Filamentous Actin - F-Actin l F-Actin is polar + and - end l Actin binding proteins Tropomyosin- Troponins (TnT, TnC, TnI) Nebulin  -actinin

4. Actin Tropomyosin/Troponin  Fig 16-39 p. 542  Tropomyosin is a filamentous protein wrapped around the actin helix  Troponin Complex l Three polypeptides l Troponin C interacts with Ca +2

5. Protein components II  Thick filaments fig16-32 p. 536 l Myosin specific to skeletal muscle –Myosin heavy chains »Rod-like “tail” »Globular “head” –Myosin light chains –Myomesium - crosslinker or bundler of the M line –Titin - anchors thick filament to Z line - Spring like helping to prevent hyper-extension –C-protein binds to thick filaments at M line

6. Proteins of Sarcomere

7. Important Microanatomy  Sarcolemma - Muscle PM  Sarcoplasmic Reticulum - analogous to ER  Sarcoplasm is like cytoplasm  Tissue is synctium  T-tubes - transverse connections within the SR

8. Myosin Molecules  Fig 16-32 p 536 & Fig 16-33 p 537  Myosin I found in non-muscle cells l Moves along actin, but is not bundled  Myosin II found exclusively in muscle cells l Two globular heads per molecule l Bundled into thick filament l Globular head binds both actin and ATP

9. Myosin continued  Type two - two heavy chains l Globular heads l Hinge region l Long rod-like tail  Function - convert ATP chemical energy into mechanical force that causes actin filaments to slide past myosin molecule

10. Contraction of Skeletal Muscle  Sliding filament model l Model of how thin filaments increase overlap l Binding, hydrolysis and release of ATP--> ADP + Pi l Thin filaments slide past thick filaments and penetrate more deeply into the A band l I bans and H bands shorten as Z disks are drawn closer together

11. Sliding filament model  Initiation of contraction l Triggered by depolarization at neuromuscular junction - leads to Ca +2 release from intracellular storage (in SR) l The sarcolemma depolarizes first and the signal sweeps across the membrane and across T- tubes l T-tubes are electrically connected to SR

12. Initiation and Regulation  Ca +2 ions are released into the cytosol at the A-I junctions via Ca +2 release channels of the SR  Activation by calcium l At rest myosin binding sites on actin are partially covered by tropomyosin l Troponin I also is bound directly to actin and interferes with myosin binding

13. Activation (Switching On)  Calcium ions bind to troponin C causing a conformational change in the entire troponin complex  This breaks the TnI interaction and leads to a shift in tropomyosin  These two actions uncover myosin-actin binding sites leading to the active state

14. Relaxation (Switching Off)  Ca +2 levels eventually drop, when there is no longer stimulation  TnC loses its Ca +2  Result tropomyosin returns to original post  Relaxation is dependent upon the Ca +2 ATPase pump-  Ca +2 ATPase pump in SR is always on

15. Cardiac muscle  Contract spontaneously and display rhythmic beat  May be branched at the ends  One to two nuclei  Poorly defined myofibrils  Cross banding pattern like skeletal  Do not regenerate

16. Structural components  T-tubes are larger  SR is poorly defined  Calcium ions During relaxation leaks into sarcoplasm In response voltage gates release Ca+2 from SR Force of contraction is directly related to [Ca+2]  Mitochondria are abundant

17. Cardiac Muscle  Cells maintain their individuality  They are linked physically by l Fascia adherens l Desmosomes  They are linked electrically by l Gap junctions

18. Structural Components of Cardiac Muscle

19. Intercalated disk  Step like structure  Interdigitation of cardiac muscle cells  Transverse section Desmosomes Fascia adherens (z- disk anchor)  Longitudinal region l Gap junctions - makes cardiac muscle a functional syncytium

20. Smooth Muscle  Structure of Smooth Muscle l Spindle shaped l Not as organized as striated muscle l Numerous actin filaments anchored to dense bodies within the cytoplasm and sarcolemma(func. Equivalent Z-disk) l Intermediate fils. Desmin & Vimentin Form links between dense bodies

21. Smooth Muscle  In addition to the other general structural features smooth muscle has Gap junctions (nexus) in the sarcolemma

22. Contraction of Smooth Muscle

23. Smooth Muscle Contraction  Involves stimulus form nerve or hormome  Ca +2 ions are pumped outside the cell and allowed back in to initiate a contraction  Ca +2 interacts with small regulatory protein called calmodulin  Ca-Calmodulin activate MLCKinase

24. Smooth Muscle Contraction  MLCKinase - phosphorylates light chains of Myosin II of smooth muscle  This activates myosin II  Contraction begins l More slowly  Contraction releases more gradually  Many different mechanisms

25. Innervation of Smooth Muscle  Sympathetic nerves l Noradrenergic  Parasympathetic nerves l Cholinergic

26. Structure of NM Junction  Motor end plate or myoneural junction  Sarcolemma has numerous deep junctional folds  AP invades motor end plate l Acetylcholine is released from axon terminals l Binding to gated channels makes sarcolemma l Result membrane depolarization

27. Neuromuscular junctions

28. Neuromuscular junction 2  Components l Axon terminals l Synaptic cleft l Muscle cell has Sarcolemma invaginations Acetylcholine receptors Sacoplasm rich in mitochondria, ribosomes

29. Conduction of Nerve Impulse  Pre-synaptic membrane events l Similar to neuronal synapse when AP arrives  Post-synaptic membrane events l AP is initiated in similar manner l Conduction is more sophisticated involving sarcolemma and T-tubes l Eventual release of Ca +2 from SR

30. Acetylcholine signal  The neurotransmitter acetylcholine has a transient effect l Acetylcholinesterase is found in the external lamina lining the junctional folds l Choline is recycled by active transport uptake by transport protein found in the axon terminals

31. Sources of Energy Utilized  ATP is generated by several metabolic pathways  Potential high energy phosphates may also be stored  There is a hierarchy of most efficient sources of ATP and least efficient sources

32. Sources of Energy Utilized 2  Aerobic respiration is the most efficient means of generating large amounts of ATP  It includes: l Glycolysis l TCA cycle l Electron Transport System  When Respiration is used muscle tissue yields 36 ATP per glucose

33. Sources of Energy Utilized 3  Anaerobic conditions frequently arise l Even though muscle has a protein that can store O 2 ; namely myoglobin l O 2 is rapidly depleted under any strenuous exercise l Glycolysis is utilized, but pyruvate must be converted to lactic acid in order to keep the glycolytic pathway running

34. Sources of Energy Utilized 4  Anaerobic use of glycolysis yields l ONLY 2 ATP / glucose l Much less efficient  A high energy phosphate containing compound creatine phosphate can be used to take ADP to ATP  Finally myokinase can take 2ADP --> ATP + AMP