Skeletal muscle in the light of its structure
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1 Mechanism of contraction of Skeletal muscle in the light of its structure By Dr. Mudassar Ali Roomi (MBBS, M. Phil)
2 Muscle Tissue Skeletal Muscle Cardiac Muscle Smooth Muscle
3 Skeletal Muscle Long cylindrical cells Many nuclei per cell Striated Voluntary Rapid contractions
4 Cardiac Muscle Branching cells One or two nuclei per cell Striated Involuntary Medium speed contractions
5 Smooth Muscle Fusiform cells One nucleus per cell Nonstriated Involuntary Slow, wave-like contractions
6 Skeletal muscle
7 SKELETAL MUSCLE
8 Z line Z line
9 THICK AND THIN FILAMENTS From surface of thick filaments projections arise cross-bridges. In centre of sarcomere, thick filaments have no projections (H zone). The thin & thick filaments contain contractile proteins: The thick filaments contain myosin protein. The thin filaments contain actin, tropomyosin & troponin proteins.
10 Myosin protein: in thick filaments In 1 thick filament 200 myosin molecules. Molecular wt. of each myosin molecule = 480,000. Each myosin molecule has 6 polypeptide chains: 2 heavy chains & 4 light chains. 2 heavy chains are coiled together double helix. At 1 end two heavy chains are folded head portion. In head portion 4 light chains.
11 Myosin protein: in thick filaments (cont ) 3 parts of myosin molecule: Head Arm / Neck Body / Tail There are 2 points in myosin molecule at which molecule is highly flexible HINGES: i) Between head & arm / neck ii) Between arm & body / tail Tail/body is present in thick filaments. Arm & head protrude out from surface of filament as cross bridges.
12 Myosin protein: in thick filaments (cont ) Cross bridges are absent in centre. In the centre of filament is tail only, while cross bridges are formed by arm & head at periphery as cross bridges. In myosin head there are 2 important sites: Actin binding site. Catalytic site.
13 Thin filaments 3 contractile proteins are present here: 1) ACTIN: Consist of 2 F-actin strands. Each strand consist of polymerized G actin molecules. Attached to each G actin molecule is a molecule of ATP, & point of attachment is active site on actin strand. Active sites are present at every 2.7 nm. Each G actin has molecular wt. 42,000.
14 Thin filaments (cont ) 2) TROPOMYOSIN: Consist of 2 strands, with 70,000 molecular wt. Tropomyosin strands at rest physically cover active sites on actin filaments. 3) TROPONIN: Attached to tropomyosin at intervals. It has 3 components: Troponin C, Troponin T, Troponin I. Molecular wt. 18,000 35,000.
15 Thin filaments (cont ) Troponin C Affinity for calcium ions. Troponin T Affinity for tropomyosin. (through which troponin complex is attached to tropomyosin) Troponin I Affinity for actin strands. It is the bond between troponin I & Actin, which keeps tropomyosin strands in such a position that these physically cover active sites of actin filaments. During muscle contraction this bond is broken. Tropomyosin-troponin complex = relaxing protein (keeps muscle relaxed by covering physically the active sites).
16 Components of Troponin (C,T,I)
17 Molecular Mechanism of skeletal muscle Muscle is first excited or depolarized and then contratcs (EXCITATION-CONTRACTION COUPLING). Action potential enters deep into muscle fiber from T-Tubules around which are terminal cisternae. So depolarization spreads from T Tubules terminal cisternae. Membrane of terminal cisternae is depolarized opening of voltage gated calcium channels calcium ions move out of the terminal cisternae. contraction:
18 SKELETAL MUSCLE
19 When it is in sarcoplasm, calcium is utilized by troponin C to initiate muscle contraction (excitation-contraction coupling). 4 calcium ions can bind with 1 molecule of troponin C it breaks the bond between troponin I & Actin tropomyosin strands become loose they reach a deeper position active sites on actin are uncovered.
20 Muscle contraction involves power strokes. Before contraction, a molecule of ATP becomes attached to myosin head. It is hydrolyzed to ADP to liberate energy stored in myosin head. When active site is uncovered myosin head binds with active site on actin. With stored energy, there is power stroke. At hinges, myosin molecule moves & carries along actin / thin filaments.
21
22 With energy of 2 nd molecule of ATP, it detaches & move back to original position 2 nd power stroke a series of power strokes sliding of actin over myosin so that power stroke is towards centre of sarcomere shortening of sarcomere or contraction of muscle. Each cross bridge operates independently. Greater the number of cross bridges coming in contact with myosin head greater is force of contraction. When muscle is stretched more number of cross bridges attached with actin filaments increased contraction force.
23 Binding Site Tropomyosin Troponin
24 Myosin
25
26 FRANK-STARLING LAW: Greater the initial length of muscle, greater is force of contraction up to certain limits. Cardiac muscle also obeys this law ( increased venous return increased length of cardiac muscle increased filling increased emptying by contraction of ventricle.
27 Contraction is initiated by calcium ions. As long as calcium ion is sufficient in sarcoplasm muscle contraction continues. Normally in the wall of longitudinal tubule, there is calcium pump. Calcium is released from terminal cisternae but is pumped back by calcium pump & when calcium is low in sarcoplasm muscle relaxes. So, even to produce muscle relaxation, we need ATP because calcium pump needs ATP.
28 Sarcomere Relaxed
29 Sarcomere Partially Contracted
30 Sarcomere Completely Contracted
31 SLIDING FILAMENT MODEL OF MUSCLE CONTRACTION
32 Histological changes during muscle contraction: RELAXED MUSCLE: µm length of sarcomere. AFTER CONTRACTION: µm length of sarcomere. Length of A band constant. Length of I band constant. Z Membranes become closer. H zone decreases / disappear Sliding of thin over thick filaments. Length of individual filaments remain the same.
33
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