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
Organization of the contractile machinery in smooth muscle Dense body made of alpha actinin attaches actin to actin Dense plaque attaches actin to sarcolemma
In smooth muscle Ca2+ controls contraction through a soluble Ca2+ 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)
Ca2+ can come from external or internal sources • External: entry across the cell surface through L Ca2+ channels – this is an electromechanical process • Internal: release from internal stores (endoplasmic reticulum) caused by 2nd message – this is a pharmacomechanical process.
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)
Relaxation requires both removal of Ca2+ and dephosphorylation of MLC • Ca2+ is removed by Ca2+pumps in ER and cell surface. • Dephosphorylation of MLC is by myosin light chain phosphatase.
Acetylcholine turns on intestinal smooth muscle through a 2-pronged 2nd 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 Ca2+ channels • phosphoinositol trisphosphate (IP3) which diffuses in cytoplasm and releases Ca2+ from endoplasmic reticulum
Phospholipase C splits off the “tails” of the phospholipid as DAG, and adds a phosphate to the “head” to form IP3
Epinephrine turns off intestinal smooth muscle through a cAMP 2nd message • Binding of Epi to Beta2 receptor initiates cAMP 2nd message • cAMP activates Protein Kinase A (PKA) • PKA phosphorylates MLCK • Phosphorylated MLCK cannot be activated by Ca2+-calmodulin
Norepinephrine Beta adrenergic receptor cAMP PKA MLCK-P (inactive)
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