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Outline of Lecture on Muscle Physiology 2010 (with focus on Physiology of Skeletal Muscle Contraction) Lecturer: D.G. Simbulan, Jr., Ph.D. -----------------------------------------------------------------------------------------------------------Introduction: Types and Function of Muscle Tissue I. Muscle Architecture: Review of Skeletal Muscle Fiber Structure and Filaments; Molecular Composition a. From Muscle to Fascicles to Muscle Fibers (Myofiber) to Myofibrils to Sarcomeres/Myofilaments b. What constitutes a Muscle Fiber ? Sarcolemma, Sarcoplasmic reticulum and Myofibrils c. Myofibrils and Sarcomeres; Myofilaments - Thick and Thin Filaments; What proteins constitute the thick and thin filaments; relation to each other ? Know the A-band, I-band, H-zone, M-line/region, Z-line/ disk. d. How are actin filaments anchored to the Z-line ? Role of Nebulin in stabilizing the actin filaments e. How are Myosin filaments stabilized to the Z-line/disk ? to the M line/ M-region ? Role of Titin f. Molecular structure of Actin; Myosin; acessory or regulatory proteins of actin: troponin, tropomyosin g. The T-system (transverse tubules), SR, terminal cisternae of SR, and relation to Sarcomeres; the DHP receptor in the T-tubules; the Ryanodine receptor in the terminal cisternae; which receptor is the voltage-sensor in ExcitationContraction coupling ? which receptor is the Ca++ release channel ? what is the triad ? h. Role of calsequestrin (mainly skeletal muscle, also cardiac and smooth) and calreticulin (mainly high concentration , smooth musde) in the sarcoplasmic reticulum; Ca++ pump in the SR/ terminal cisternae i. What makes calsequestrin unload its Ca++ ? II. How Does Skeletal Muscle Perform its Contractile Functions Having known muscle cytoarchitecture and molecular structure, you should be able to discuss the following: A. Excitation-Contraction Coupling a. Describe how wave of depolarization from the sarcolemma initiates muscle contraction. b. Describe relationship of DHP receptor and the Ryanodine receptor. c. Role of intracellular stores of Ca++ in SR/terminal cisternae B. Sliding Filament Theory of Muscle Contraction a. Role of thick and thin filaments b. Role of Ca++ c. Take note of the various stages/ states of the cross-bridge cycle (Berne and Levy, 5th edition, Fig. 12-11, p. 232 ). Optional see also Fig. 9-7 (Boron, p. 239). [Compare this with Figure 58-6, p. 720, Harper’s Biochemistry, note that you have to change the numbering of the steps to coincide with that of Boron (Fig. 9-7, p. 239). To do that, read the descriptions in Boron and Harper’s and the chemical reactions taking place. This is so you don’t get confused in reviewing for your Physiology and Biochemistry component of the Evals. C. Termination of Contraction; a. role of ATP b. role of Ca++ pump c. role of neuro-muscular junctional transmission What happens during muscle fatigue/ cramps ? during rigor mortis ? why ? III. Overview: Comparative Physiology of Skeletal, Cardiac, and Smooth Muscles 1. Role of calcium in initiating muscle contraction in the three muscle types 2. Where does calcium come from in the initiation of skeletal muscle contraction ? Where does calcium come from, in the initiation of cardiac and smooth muscle contraction ? 3. Principal calcium sensors in striated muscle which initiates muscle contraction ? 4. Principal calcium sensor in smooth muscle which initiates muscle contraction 5. For summary tables: see also a. Table of Some Differences Among Different Muscle Types (Harper’s Biochemistry, 25th edition, p. 725) b. Summary of Comparisons Between Muscle Types (Boron, Medical Physiology, p. 253). Others: Be able to tie up this lecture module with the Lecture topics on Electrophysiology I (Resting Membrane Poténtials and Action Potentials) and Electrophysiology II (Synaptic and Junctional Transmission). See also Table 3-2 Sequence of Events in Contraction and Relaxation of Skeletal Muscle, p. 70 in Ganong (21st/ 22nd edition, or earlier editions) , Review of Medical Physiology. References: Principally: *Guyton and Hall, Chapter 6 Contraction of Skeletal Muscle, pp. 72 – 83 Secondarily, for comparison with smooth and cardiac muscle, see: *Guyton and Hall, Chapter 8 Contraction and Excitation of Smooth Muscle, pp. 92 – 99 *Guyton and Hall, Chapter 9 Contraction and Excitation of Smooth Muscle, pp. 103 - 104 See also pre-lecture Handout for other references. Main: Berne and Levy, PHYSIOLOGY, 5th edition, Chapter 12 Boron and Boulpaep, Chapter 9, “Cellular Physiology of Skeletal, Cardiac and Smooth Muscle,”MEDICAL PHYSIOLOGY pp. 230 – 254. Ganong, Chapter 3, Ëxcitable Tissue: Muscle, pp,. 65 – 85, with focus on Skeletal Muscle, pp. 65 – 78