1. Visceral Muscle

2. How is the gut organized anatomically?

3. The two major gut plexi contain motor neurons, interneurons and sensory neurons. This diagram doesn’t show it, but many of the chemoreceptors are enteroendocrine cells (modified epithelial cells). There are approximately as many neurons in the gut as in the CNS

4. What do smooth muscle cells look like?

5. Dense plaque attaches actin to sarcolemma Organization of the contractile machinery in smooth muscle Dense body made of alpha actinin attaches actin to actin

6. In smooth muscle Ca 2+ controls contraction through a soluble Ca 2+ binding protein and a soluble kinase Contractile machinery of all muscle consists of actin (thin) filaments to which force is applied by myosin (thick) filaments which project heads (crossbridges). Control is exercised at the thin filaments in striated muscle (skeletal and cardiac), but primarily at the thick filaments in smooth muscle. The calcium-binding molecule in smooth muscle is a soluble protein, calmodulin. The protein that controls the activity of myosin heads is myosin light chain kinase (MLCK)

7. Ca 2+ can come from external or internal sources External: entry across the cell surface through L Ca 2+ channels – this is an electromechanical process Internal: release from internal stores (endoplasmic reticulum) caused by 2 nd message – this is a pharmacomechanical process.

8. The sequence of events in thick filament control in smooth muscle Ca ++ binds to calmodulin Ca ++ -calmodulin binds to MLCK MLCK-CM-Ca ++ phosphorylates myosin regulatory light chain Head associates with actin and begins to cycle Cycling continues until Pi is removed by myosin light chain phosphatase (MLCP)

10. Relaxation requires both removal of Ca 2+ and dephosphorylation of MLC Ca 2+ is removed by Ca 2+ pumps in ER and cell surface. Dephosphorylation of MLC is by myosin light chain phosphatase.

11. Acetylcholine turns on intestinal smooth muscle through a 2-pronged 2 nd message Muscarinic receptor is coupled to Phospholipase C (PLC) attached to cytoplasmic side of plasma membrane. PLC converts phosphatidylinositol bisphosphate (a membrane phospholipid) into –diacylglycerol (DAG) which diffuses in PM, closes ‘rest’ K + channels and thus activates voltage-sensitive L Ca 2+ channels –phosphoinositol trisphosphate (IP 3 ) which diffuses in cytoplasm and releases Ca 2+ from endoplasmic reticulum

12. Phospholipase C splits off the “tails” of the phospholipid as DAG, and adds a phosphate to the “head” to form IP 3

13. Epinephrine turns off intestinal smooth muscle through a cAMP 2 nd message Binding of Epi to Beta 2 receptor initiates cAMP 2 nd message cAMP activates Protein Kinase A (PKA) PKA phosphorylates MLCK Phosphorylated MLCK cannot be activated by Ca 2+ -calmodulin

14. MLCK-P (inactive) PKA Beta adrenergic receptor cAMP Norepinephrine

15. Important points In smooth muscle, force modulation is the result of changes in the number of cycling myosin heads – this can be achieved in several different ways Smooth muscle is adapted to deliver force over a wide range of working lengths