1. ANNOUNCEMENTS Review Session this Friday: 12:20 Morrill 349 IMAGE523 Poster Team: Let’s Meet After Class Write Abstract Poster Design Discussion: Exam, Midsemester Review

4. Needs Improvement Pace of class meeting (12) More explanation/detail on ppt slides (5) Lab/Lecture Linkage (4) More dental coverage (2) Many other thoughtful ideas (1) limit reading more previous exams figures in lab guide lab more hands-on more graded assignments and others

5. Structure - Function Muscle Contraction StriatedNonstriated SkeletalSmooth Cardiac

6. Striated Muscle: Sarcomere

7. Striated Muscle: Sarcomere- Z line to Z line Z line

8. Sarcomere Z line to Z line A band I band M line H band

9. Thin filaments – Microfilaments (Actin) – Anchored to Z line by  -actinin, nebulin – Associated with Troponin, Tropomyosin, Tropomodulin Thick filaments - Myosin: 2 Heavy / 4 light chains - Anchored to Z line by Titin - M line anchors: myomesin and C-proteins Molecular Components of Sarcomere

11. This is an electron micrograph of a section through a sarcomere of a skeletal muscle fiber. Where in the sarcomere is the section taken?

14. Striated Muscle Contraction Thin Filament Tropomyosin: – winds around actin – obscures actin-myosin binding site Troponin Complex – Troponin T: interacts with Tropomyosin – Troponin I: prevents myosin-actin binding – Troponin C: binds Ca++, allowing myosin-actin binding

17. Striated Muscle Contraction Thin Filament Tropomyosin Troponin – Troponin T – Troponin I – Troponin C Ca +2

20. Contraction of Striated Muscle - Release of Calcium from Sarcoplasmic Reticulum - Calcium binds to Troponin - Tropomyosin/Troponin shift to expose binding site - Myosin head binds to Actin; Pi released - Release of ADP from Myosin ---> POWERSTROKE - Binding of ATP: Myosin detaches from Actin - Splitting of ATP---> ADP + PI; Myosin head is reset

21. http://www.sci.sdsu.edu/movies/actin_myosin.html

22. Excitation-Contraction Coupling T tubules Sarcoplasmic reticulum: Calcium Triads Sarcoplasmic Reticulum and T-tubules

23. T-tubules

24. Sarcoplasmic Reticulum Triad

27. Striated Muscle Structure T tubules Sarcoplasmic reticulum: Calcium Triads: juncture of T-tubules & SR - Must release calcium from sarcoplasmic reticulum to initiate the contraction process. Excitation-Contraction Coupling

28. Muscle Action Potential Transverse Tubules Sarcoplasmic Reticulum Calcium release

29. Excitation-Contraction Coupling Muscle Action Potential Transverse Tubules Sarcoplasmic Reticulum Calcium release

30. http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Ryanodine/receptors.jpg T-tubule membrane

31. Smooth Muscle Contraction -No organized sarcomere structure -Actin filaments are associated with tropomyosin but Not Troponin What controls actin-myosin interaction?

32. Smooth Muscle Contraction -Myosin interacts with actin only when the myosin light chains are phosphorylated

33. Smooth Muscle Excitation-Contraction 1) Excitation=> Ca ++ influx 2) Ca ++ binds Calmodulin 3) Ca ++ -Calmodulin activates myosin light chain kinase (MLCK ) 4) MLCK phosphorylates myosin light chains 5) Myosin binds actin => contraction

35. Regulation of Smooth Muscle Contraction Nonneural regulation Hormonal: Oxytocin- uterine contraction Nitric Oxide (NO): Produced by endothelial cells of arterioles Relaxes smooth muscle

36. Mice have been produced whose eNOS (endothelial cell NO synthase) genes been "knocked out”. Predict the blood pressure levels of these mice.

37. Nitric Oxide ----> increased [cGMP] activates a kinase inhibits Ca ++ influx into smooth muscle cell decreased calcium-calmodulin stimulation of MLCK decreased phosphorylation of myosin light chains decreased smooth muscle tension development vasodilation (expansion of vessel lumen)

38. Nitric Oxide ----> increased [cGMP] activates a kinase inhibits Ca ++ influx into smooth muscle cell decreased calcium-calmodulin stimulation of MLCK decreased phosphorylation of myosin light chains decreased smooth muscle tension development vasodilation (expansion of vessel lumen) What would be the effect of drugs that inhibit the breakdown of cGMP ?

39. Drugs that inhibit the breakdown of cGMP potentiate (increase) the effects of NO actions on target cells. EXAMPLE: Viagra and other inhibitors of cGMP-dependent phosphodiesterase

40. Innervation of Muscle Smooth Muscle Innervation: boutons en passant acetylcholine Stimulation spread by gap junctions

41. Innervation of Smooth Muscle A multiunit system: fine innervation for regulation of individual cells; cells that control the iris opening A single unit system: 1 neuromuscular Junction serves a sheet of muscle fibers; stimulus transmitted to other Muscle cells via gap junctions; wall of intestine

42. Innervation of Striated Muscles Skeletal Muscle: each muscle fiber has at least 1 neuromuscular junction Cardiac Muscle: contract spontaneously rate governed by innervation excitation spread by gap junctions

43. Motor Neuron Nerve Action Potential Synapse Neuromuscular Junction Neurotransmitter (ACh) Receptors (AChR) Muscle Action Potential Transverse Tubules Sarcoplasmic Reticulum Calcium release

44. Neuromuscular Junction Nerve stimulation Action potential Opening of calcium channels Exocytosis of synaptic vesicles Acetylcholine release Binding to Acetylcholine receptors (AChR) Muscle depolarization including T-tubules Opening of Calcium channels in SR

45. Motor endplate=Neuromuscular Junction Synaptic vesicles Active zones Junctional folds AChR (acetylcholine receptor) clusters Schwann cell

47. Junctional Folds

50. Types of skeletal muscles Fast muscles – Strong and rapid contraction; rapid fatigue – ATP from anaerobic glycolysis – Phasic motor neuron Slow muscles – Slower but sustained contraction – ATP from oxidative respiration (mitochondria) – Tonic motor neuron

51. http://www.lionden.com/muscle_animations.htm Stain for ATPase activity: dark-->faster contracting

52. Synaptic input influences properties of muscle fibers Calcineurin Activates NFAT (nuclear factor of activated T cells) Transcription of slow muscle program