WINDSOR UNIVERSITY SCHOOL OF MEDICINE

1. WINDSOR UNIVERSITYSCHOOL OF MEDICINE Smooth Muscle Dr.VishalSurender.MD.

2. Smooth Muscle: Properties • Each fibre is much smaller than in skeletal muscle • Found in walls of hollow organs and tubes. • Usually found in two different layers: • Circular – to squeeze or dilatee.g-blood vessels. • Longitudinal – to stretch or shortene.g-GI tract. Metabolic economy-Uses less energy, Low oxygen consumption thus allows to Maintain force for long periods, e.x-urinary and esophageal sphincters.

3. Smooth muscle is different:- • It has more variety • Anatomy is different. • It is controlled by hormones, paracrines, and neurotransmitters. • Unitary and Multiunit Smooth Muscle • There are two distinct categories of smooth muscle determined by the processes they use to coordinate contraction with their neighboring cells

4. Single unit/Visceral smooth muscle • This represents the majority • Made up of groups of cells joined together by gap junctions • FUNCTIONAL SYNCYTIUM • may be innervated but does not always require nervous stimulation for contraction • Allows for coordinated contractions • Uterus, GIT

5. Types of Smooth Muscle Figure 12-25a

6. Multi unit smooth muscle • Found in large blood vessels, large airways and ciliary muscle • Made up of discrete units • Similar to skeletal muscle • Must be separately stimulated by nerves • Autonomic stimulation

7. Types of Smooth Muscle Figure 12-25b

8. Smooth Muscle • Has actinand myosin filaments but Lacks the Regular Sarcomere Structure of Skeletal Muscle. • Myosin light chain hasregulatory role • Have intermediate filaments- dense bodies, analogous to Z-line • Has less sarcoplasmic reticulum • IP3-receptor channel is the primary calcium channel. • Calcium storage function of sarcoplasmic reticulum is supplemented by Caveolae analogous to ….. In skeletal muscle?

9. Caveolae in Smooth Muscle Figure 12-26

10. Anatomy of Smooth Muscle Figure 12-27a–b

11. Molecular Mechanism of Smooth Muscle Contraction. • In order for smooth muscle to contract there must be some connection between the myofilaments and the cell (to have the same role as the Z line in skeletal muscle). • This connection is provided by the dense bodies found within the smooth muscle cells. • The thick filament is made of myosin as in skeletal muscle (though of a different form) and so has two heavy chains, including the crossbridge region with the 4 light chains found on the heads. These light chains have an important role to play in smooth muscle contraction because it is phosphorylation of the regulatory light chains found on the myosin heads that initiate contraction. • When the myosin is phosphorylated it binds to the thin filaments and pulls them towards the center of the thick filament moving the two dense bodies connected to the thin filaments closer together, shortening the smooth muscle cell.

12. ECF Ca2+ Sarcoplasmic reticulum 1 Intracellular Ca2+ concentrations increase when Ca2+ enters cell and is released from sarcoplasmic reticulum. 1 Ca2+ Ca2+ Pi CaM 2 Pi 2 Ca2+ binds to calmodulin (CaM). Ca2+ CaM Inactive MLCK 3 3 Ca2+–calmodulin activates myosin light chain kinase (MLCK). Active MLCK ATP 4 P ADP + 4 MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity. P Inactive myosin Active myosin ATPase Actin Active myosin crossbridges slide along actin and create muscle tension. 5 5 Increased muscle tension Smooth Muscle Contraction Figure 12-28

13. ECF Ca2+ Sarcoplasmic reticulum 1 Intracellular Ca2+ concentrations increase when Ca2+ enters cell and is released from sarcoplasmic reticulum. 1 Ca2+ Ca2+ Smooth Muscle Contraction Figure 12-28, step 1

14. ECF Ca2+ Sarcoplasmic reticulum 1 Intracellular Ca2+ concentrations increase when Ca2+ enters cell and is released from sarcoplasmic reticulum. 1 Ca2+ Ca2+ Pi CaM 2 Pi 2 Ca2+ binds to calmodulin (CaM). Ca2+ CaM Smooth Muscle Contraction Figure 12-28, steps 1–2

15. ECF Ca2+ Sarcoplasmic reticulum 1 Intracellular Ca2+ concentrations increase when Ca2+ enters cell and is released from sarcoplasmic reticulum. 1 Ca2+ Ca2+ Pi CaM 2 Pi 2 Ca2+ binds to calmodulin (CaM). Ca2+ CaM Inactive MLCK 3 3 Ca2+–calmodulin activates myosin light chain kinase (MLCK). Active MLCK Smooth Muscle Contraction Figure 12-28, steps 1–3

16. ECF Ca2+ Sarcoplasmic reticulum 1 Intracellular Ca2+ concentrations increase when Ca2+ enters cell and is released from sarcoplasmic reticulum. 1 Ca2+ Ca2+ Pi CaM 2 Pi 2 Ca2+ binds to calmodulin (CaM). Ca2+ CaM Inactive MLCK 3 3 Ca2+–calmodulin activates myosin light chain kinase (MLCK). Active MLCK ATP 4 P ADP + 4 MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity. P Inactive myosin Active myosin ATPase Smooth Muscle Contraction Figure 12-28, steps 1–4

17. ECF Ca2+ Sarcoplasmic reticulum 1 Intracellular Ca2+ concentrations increase when Ca2+ enters cell and is released from sarcoplasmic reticulum. 1 Ca2+ Ca2+ Pi CaM 2 Pi 2 Ca2+ binds to calmodulin (CaM). Ca2+ CaM Inactive MLCK 3 3 Ca2+–calmodulin activates myosin light chain kinase (MLCK). Active MLCK ATP 4 P ADP + 4 MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity. P Inactive myosin Active myosin ATPase Actin Active myosin crossbridges slide along actin and create muscle tension. 5 5 Increased muscle tension Smooth Muscle Contraction Figure 12-28, steps 1–5

18. Calcium Plays a Critical Role in Smooth Muscle Activation

19. Smooth Muscle Contraction Activating MLCK Ca2+ myosin-Pi myosin +ATP/actin CONTRACTION

20. Ca2+ Ca2+ Na+ ECF ATP Free Ca2+ in cytosol decreases when Ca2+ is pumped out of the cell or back into the sarcoplasmic reticulum. 1 Sarcoplasmic reticulum 1 Na+ Ca2+ ATP Ca2+ Ca2+ unbinds from calmodulin (CaM). 2 CaM 2 Myosin phosphatase removes phosphate from myosin, which decreases myosin ATPase activity. 3 Ca2+ CaM Myosin phosphatase 3 ATP Less myosin ATPase results in decreased muscle tension. 4 P ADP + P Inactive myosin Myosin ATPase activity decreases. 4 Decreased muscle tension Relaxation in Smooth Muscle Figure 12-29

21. Ca2+ Ca2+ Na+ ECF ATP Free Ca2+ in cytosol decreases when Ca2+ is pumped out of the cell or back into the sarcoplasmic reticulum. 1 Sarcoplasmic reticulum 1 Na+ Ca2+ ATP Ca2+ Relaxation in Smooth Muscle Figure 12-29, step 1

22. Ca2+ Ca2+ Na+ ECF ATP Free Ca2+ in cytosol decreases when Ca2+ is pumped out of the cell or back into the sarcoplasmic reticulum. 1 Sarcoplasmic reticulum 1 Na+ Ca2+ ATP Ca2+ Ca2+ unbinds from calmodulin (CaM). 2 CaM 2 Ca2+ CaM Relaxation in Smooth Muscle Figure 12-29, steps 1–2

23. Ca2+ Ca2+ Na+ ECF ATP Free Ca2+ in cytosol decreases when Ca2+ is pumped out of the cell or back into the sarcoplasmic reticulum. 1 Sarcoplasmic reticulum 1 Na+ Ca2+ ATP Ca2+ Ca2+ unbinds from calmodulin (CaM). 2 CaM 2 Myosin phosphatase removes phosphate from myosin, which decreases myosin ATPase activity. 3 Ca2+ CaM Myosin phosphatase 3 ATP P ADP + P Inactive myosin Myosin ATPase activity decreases. Relaxation in Smooth Muscle Figure 12-29, steps 1–3

24. Ca2+ Ca2+ Na+ ECF ATP Free Ca2+ in cytosol decreases when Ca2+ is pumped out of the cell or back into the sarcoplasmic reticulum. 1 Sarcoplasmic reticulum 1 Na+ Ca2+ ATP Ca2+ Ca2+ unbinds from calmodulin (CaM). 2 CaM 2 Myosin phosphatase removes phosphate from myosin, which decreases myosin ATPase activity. 3 Ca2+ CaM Myosin phosphatase 3 ATP Less myosin ATPase results in decreased muscle tension. 4 P ADP + P Inactive myosin Myosin ATPase activity decreases. 4 Decreased muscle tension Relaxation in Smooth Muscle Figure 12-29, steps 1–4

25. Smooth Muscle Relaxation Myosin light chain phosphatase predominates Deactivating MLCK Ca2+ myosin-Pi myosin RELAXATION

26. Smooth Muscle Regulation • Many smooth muscles have dual innervation • Controlled by both sympathetic and parasympathetic neurons • Hormones and paracrines also control smooth muscle contraction • Histamine constricts smooth muscle of airways • Nitric oxide affects regulation of diameter of blood vessels

27. Muscles: Summary