Smooth muscle characteristics:
--short, tapered on the end, 40-600 microns long
--only one nucleus per cell
--dense bodies ("so called") are where actin attaches (as opposed to Z lines in skeletal) and are both on membrane and dispersed throughout cells
--intermediate filaments link dense bodies, transmit force of contraction
--no striations because sarcomeres don't line up (they attach to dense bodies not Z lines)
--has myosin but it's different: no troponin and has "sidepolar" cross bridge arrangements, so that it can pull actin in opposite directions on each side of the polymer, allowing SM cell to contract as much as 80% of their length (skeletal can only contract about 30% of its length)
--"dense area" (Brons) on membrane (same as dense body?) links adjacent cells (I think he means dense bodies) (are gap junctions associated with dense bodies???)
--gap junctions allow free flowing communication between cells, create syncytium
--syncytium = many cells working together as one unit, in smooth and cardiac muscle cells contract together (cytoplasm together)
--connexins = gap junction proteins
--two types of function: unitary and multiunit
--contraction depends on phosphorylation of myosin light chain, myosin functions as an ATPase called myosin light chain kinase (MLCK) which is activated by Ca++ and calmodulin
--myosin phosphatase removes the inorganic phosphate from a latched myosin and releases it.
Contraction cycle is 1/10 to 1/300 the speed of skeletal muscle, requiring correspondingly less energy. Only one ATP is required for each cycle, regardless of its duration. Total contraction time (unless latched) is 1-3 seconds. Much greater force is generated by smooth muscle than skeletal, as great as 4-6 kg/cm3, due to prolonged period of actin-myosin attachment and longer myosin strands offering more simultaneous attachments.
1. Ca++ binds with calmodullin
2. Ca-calmodulin combo joins with and activates myosin kinase (a phosphorylating enzyme)
3. Myosin kinase (MLCK) phosphorylates the regulatory light chain on each myosin head. When this chain is not phosphorylated, the actin/myosin cycle does not occur. When it is phosphorylated, the head can bind repeateadly with actin and pull pull pull.
4. ATP is degraded to ADP when a myosin head detaches from actin (so when it's latched it doesn't detach and doesn't degrade ATP)
1. at rest ATP is hydrolyzed
2. myosin*ADP*P binds to actin (MLCK, myosin kinase?)
3. cross bridges bend when ADP*P are released (power stroke?)
4. crossbridges detach when ATP binds to myosin (detachment?)
Need Ca++ in cell to contract, sources:
1. brought in from outside cell
a. via voltage-gated channels (charge from local AP or ANS)
b. via ligand-gated channels (G-proteins) (opened by hormones or neurotransmitters)
2. released from sarcoplasmic reticulum (ligands trigger formation of IP3 that triggers SR Ca++ release)
Latch State: at full contraction, little signal or energy are required for muscles to remain contracted, myosin linked to actin.
--when myosin kinase and myosin phsophatase enzyumes are both strongly activated, the cycling frequency of myosin heads and velocity of contraction are great. As the activation of the enzymes decreases, the cycling frequency decreases, but the myosin heads can remain attached to the actin filament for a longer and longer part of the cycle. The number of heads attached to the actin at any given time is large. Because the number of heads attached determines the static force of contraction, tension is maintained, yet little energy is used because there's no cycling going on.
--P is removed from myosin light chain, reduces cycling rate and causes continuous contraction
--uses little ATP and Ca++, MLCK inactive
--sphincters work this way
--increase Ca++ and bring in P to release muscle in latch state only ???
--when Ca++ ion concentraction falls below a critical level, contraction automatically reverses, except for the phosphorylation of the myosin head.
--myosin phosphatase is required to split phosphate from the regulatory light chain, then cycling stops and contraction ceases. Time it takes to relax depends on amount of active myosin phosphatase in the cell.
1. Ca++ uptake by SR-pumps lowers LCMK activity
2. Ca-calmodulin dissociates from light chain myosin kinase
a. NE vasodilates coronary blood vessels via beta2 receptors, cAMP kinase inhibits phosphyrlation of light chains by Ca++ slowing cycling rate ???
b. NO activates PKC that inhibids Ca-calmodulin vasodilation ???
Unitary (or single unit or visceral) smooth muscle = One cell in each bundle is innervated, or varicosities in axon form diffuse junctions that communicate with outer layer of bundle. All cells in bundle are linked by gap junctions into syncytium. Action is either phasic or tonic action.
--phasic = rhythmic contractions, ie peristalsis in GI and UG systems, AP's are propagated thru tissue
--tonic = continuous contraction, ie in sphinters, urinary bladder, gallbladder, blood vessels & airways, responds to graded membrane potential fluctuations
Multiunit smooth muscle = not coupled by gap jcts, separate neuromuscular junction for each cell, found in iris of eye, ductus deferens
--active tension is proportional to number of cross bridges
--active filaments are longer in smooth muscle. With stretch, actin and myosin separate, but more cross bridges maintain tension over wider lengthening.
--passive tension due to viscoelastic materials (CT, hyaluronic acid gel between cells, and presence of non-cycling cross bridges ie latch)
--smooth muscle contraction is slower than skeletal
--myosin isomer has lower ATP-ase activity
--velocity unnecessary since SM load is organ pressure; tension is maintained by tonic contraction
--velocity can increase by phosphyrlation of myosin light chains which increases cross-bridge cycling
--smooth muscle is like type I slow skeletal muscle, in which oxidative phosphorylation ismore important than anaerobic glycolysis
Phenotypic shifting (good and bad)
--smooth muscle adapts to changing conditions
--prenancy: high progesterone & estrogen levels & stretch alter uterine smooth muscle, hypertrophy (polyploidy leads to more synthesis of actin & myosin), more gap junctions facilitate coordination contractions in parturition
--hypertension: high tension of vascular wall triggers myogenic contraction and induces hypertrophy with aggravates the hypertension, and phenotypic transformation in which SM becomes CT and looses contractility. Golgi appartus and rER replace myofilaments.