1. MUSCLE PHYSIOLOGY Ass. Prof. Dr. Emre Hamurtekin EMU Faculty of Pharmacy

2. SKELETAL MUSCLE

3. STRUCTURAL PROPERTIES

8. SARCOTUBULAR SYSTEM T system and sarcoplasmic reticulum T system of transverse tubules is continous with the sarcolemma The SR has enlarged terminal cisterns at the junctions between the A and I bands. Triad T system provides a path for the rapid transmission of action potential SR is an important store of Ca

9. SARCOTUBULAR SYSTEM

10. ELECTRICAL and ION CHARACTERISTICS of SKELETAL MUSCLE Resting membrane potential: -90 mV Action potential lasts: 2-4 ms Conducted along the muscle fiber : 5 m/s Ion distribution is similar to that across the nerve cell membrane.

11. CONTRACTILE RESPONSES Muscle twitch: A brief contraction folllowed by relaxation which is caused by a single action potential.

12. MOLECULAR BASIS OF CONTRACTION In resting muscle:  Troponin I covers the sites where myosin heads interact with actin  Myosin head contains tightly bound ADP Step 1: Following an action potential, cytosolic Ca increases and binds to Troponin C Step 2: Weakening of Troponin I interaction with actin and myosin-actin cross bridges occur. Step 3: Upon formation of the cross-bridge, ADP is released. Step 4: ADP release causes a conformational change and myosin head moves the thin filament (power stroke). Step 5: ATP binds to the free site on the myosin. This leads to a detachment of the myosin head from the thin filament. Step 6: ATP is hydrolyzed and cycle is completed.

14. MOLECULAR BASIS OF CONTRACTION Excitation-contraction coupling: The process that a depolarization of a muscle fiber initiates a contraction Ca is reduced in the muscle cell by SERCA and this causes a cessation of interaction between actin and myosin Pumping of the Ca back into the sarcoplasmic reticulum causes relaxation

15. TYPES OF CONTRACTION ISOMETRICISOTONIC (same length)(same tension)

16. SUMMATION OF CONTRACTIONS Contractile mechanism does not have a refractory period. Summation of contraction: Additional contractile response that is added to the already present contraction. Tetanic contraction (tetanus): Because of the activation of contractile mechanism occurs repeatedly before any relaxation occurs, individual responses fuse into one continuous contraction. Tetanic contraction: – Complete tetanus – Incomplete tetanus

17. SUMMATION OF CONTRACTIONS

18. MOTOR UNIT Each single motor neuron and the muscle fibers it innervates constitute a motor unit. The number of muscle fibers in a motor unit varies.

19. CARDIAC MUSCLE

20. MORPHOLOGY The striations are similar to those in skeletal muscle. Z-lines are present. There are large numbers of mitochondria. The muscle fibers branch and interdigitate. Intercalated disks Muscle fiber resmi

21. MORPHOLOGY

22. Along the sides of the muscle fibers next to the disks, the cell membranes form gap junctions. Cardiac muscle function as if it was a syncytium: Intercalated disk Gap junctions T-system in cardiac muscle is located at Z-lines (not at the A - I junction).

23. ELECTRICAL PROPERTIES The resting membrane potential: -80 mV. A plateau is present before the membrane potential returns to the baseline. Cardiac myocytes contain at least 2 types of Ca channels (T- and L-types), but the Ca current is mostly due to opening of slower L- type Ca channels.

24. ELECTRICAL PROPERTIES Phase 0 initial rapid depolarization and the overshoot Phase 1 the initial rapid repolarization Phase 2 prolonged plateau Phase 3 to Phase 4 final repolarization to resting membrane potential opening of voltage-gated Na channels. closure of Na channels and opening of one type of K channel. slower but prolonged opening of voltage-gated Ca channels. closure of Ca channels and a slow delayed increase of K efflux through various types of K channels.

25. MECHANICAL PROPERTIES & METABOLISM The contractile response of cardiac muscle lasts about 1.5 times as long as the action potential. The cardiac muscle can’t be tetanized!!! Abundant blood supply, numerous mitochondria, high content of myoglobin. Normally less than 1% of the total energy is provided by anaerobic metabolism. Under basal conditions caloric needs of the heart are provided by, – 35% by carbohydrate – 5% by ketones and amino acids – 55% by fat

26. SMOOTH MUSCLE

27. MORPHOLOGY No visible cross-striations. Actin & myosin II are present and slide on each other to produce contraction. Instead of Z-lines, there are dense bodies. Contains tropomyosin but troponin is absent. Sarcoplasmic reticulum is less extensive. Contain few mitochondria.

28. MORPHOLOGY

29. TYPES A) Unitary (visceral) smooth muscle B) Multiunit smooth muscle Unitary (visceral) smooth muscle – i.e. intestine, uterus, ureter – occurs in large sheets – has many low-resistance gap-junctional connections (syncytial function) Multiunit smooth muscle – i.e. iris of the eye – individual units (few or no gap junctional bridges) – Each multiunit smooth muscle cell has endings of nerve fibres.

30. TYPES

31. ELECTRICAL & MECHANICAL ACTIVITY Unitary smooth muscle is characterized by the instability of its membrane potential. Continuous, irregular contractions (tonus) Resting potential: from -20 mV to -65 mV. Excitation-contraction coupling in unitary smooth muscle is a very slow process. Contractions of multiunit smooth muscle are more discrete, fine and localized than unitary smooth muscle contractions.

32. CONTRACTION & RELAXATION Source of Ca increase in unitary smooth muscle: – influx through voltage or ligand-gated plasma membrane channels. – efflux from intracellular stores through the RyR – efflux from intracellular stores through the IP3 receptor Ca channel. The lack of troponin: myosin must be phosphorylated for activation of myosin ATPase. – Calmodulin-dependent myosin light chain kinase

33. CONTRACTION & RELAXATION

35. Contraction Dephosphorylation of myosin by myosin light chain phosphatase Relaxation, or sustained contraction due to the latch bridge and other mechanisms

36. CONTRACTION & RELAXATION Unitary smooth muscle contracts when stretched in the absence of any extrinsic innervations unlike other types of muscle. Intestinal smooth muscle preparation: Norepinephrine (relaxation) X acetylcholine (contraction) NO-nitric oxide- (released from endothelial cells) leads to relaxation of blood vessel smooth cell.

37. THE END