Smooth Muscle Lecture Flashcards
where is SM formed?
- vasculature (particularly the arteries)
- airways (trachea, bronchi, etc)
- GI tract
- urogenital tract
- eye
functions of SM
- contract and maintain contraction for long periods of time (in vasculature and sphincters of GI tract)
- rarely fully relax
- contract periodically to mix contents of organs
- maintain shape of organ
- continue to generate active tension
- be responsive to local influences and the brain
- use relatively little ATP for energy
tropomyosin in thin filaments
- NOT primary contractor of cross bridge cycling (like it was in skeletal muscle)
- it does appear to function as a regulator of myosin ATPase
tropomyosin and calponin
- calponin is a secondary regulator of cross bridge cycling
- with calponin, increases activity of myosin ATPase
- increases rate of contraction
tropomyosin and caldesmon
- caldesmon is a secondary regulator of cross bridge cycling
- decreases rate of contraction
- may determine and control length of thin filament with caldesmon
myosin in SM
-different isoform than the one in skeletal muscle
-much slower activity
-about 1/4 of amount found in striated muscle
more loosely arranged than you would find in striated muscle
types of innervation in SM vs. skeletal muscle
- SM: multiple sources: intrinsic, ANS, sensory
- skeletal: alpha-motorneuron
NT in SM vs. skeletal muscle
- SM: ACh, Epi/Norepi, NO, other
- skeletal: ACh
excitatory/inhibitory in SM vs. skeletal muscle
- SM: may be excitatory or inhibitory
- skeletal: ONLY excitatory
contract b/w nerve and muscle in SM vs. skeletal muscle
- SM: varicosities, no MEP, receptors scattered along axon
- skeletal: NMJ
types of receptors in SM vs. skeletal muscle
- SM: multiple types of receptors:
- nicotinic/muscarinic
- adrenergic (alpha and beta)
- skeletal: ACh receptors–nicotinic cholinergic R on MEP
intrinsic innervation on SM
- innervation that arises from a nerve plexus within organ
- in the GI tract and the trachea
- contraction controlled independently of brain and spinal cord
extrinsic innervation on SM
- innervation that arises from CNS
- usually from autonomic NS
- arterial SM receives primarily sympathetic input
sensory (or afferent) innervation
- innervation arising from organ in question and traveling to brain
- senses and relays information regarding specific sensory info to brain
- often initiates reflexes in response to whatever sensory info is sensed
acetylcholine
- can cause increased activity in SM such as in gut
- may inhibit other SM
epinephrine
- causes increased activity in vascular SM
- usually relaxes GI and bronchial SM
NO
- major inhibitory signal to many systems
- acts via cGMP
- NO synthase in neurons splits arginine into NO and citrulline
what does the different actions of NT depend on?
types of receptor
-can be inhibitory or excitatory
what R are used for ACh?
- nicotinic cholinergic
- muscarinic cholinergic
what R is used for Norepi/Epi?
adrenergic (alpha and beta)
what R used for NO?
no known R
what are 2 other ways that SM can be controlled besides NT?
- stretching–especially true in vasculature
- opens channels when mechanically stretched and allow ions in
- pacemaker cells
pacemaker cells
- way of producing spontaneous activity to control SM
- seen in single unit SM–lots of gap junctions to transmit signal
NO as a paracrine agent
- known as endothelial derived relaxing factor (EDRF)
- produced by endothelium of vessels in response to high flow rate of blood
- shear stress activates stretch activated Ca channels
- inc intracellular Ca
- activates NO synthase
- very lipid soluble so can easily diffuse across membrane
prostacyclin
- derivative of AA via COX
- also called PGI2
- released by endothelial cells in vasculature
- increased shear stress
- cause an inc in intracellular Ca in endothelial cell
- leads to inc activity of Ca-ATPases which remove Ca from intracellular space
- inhibition of vascular SM
EDHF (endothelial derived hyper polarizing factor)
- may be derivative of AA from P450 pathway released in response to shear stress on vessels
- opens K channel so K leaves SM cell and causes hyper polarization of cell membrane to prevent contraction
- vasodilator in human
varicosities
- swellings in neuron where NT release occurs
- release NT in same way as skeletal muscle in that there is Ca brought into the varicosity and the fusion of vesicles with NT inside fuses to cell membrane then leads to exocytosis to release to synaptic cleft
sources of ATP for contraction
- b/c of slower cycling in general, AT usage is low in most SM
- oxidative phosphorylation can do job even with low numbers of mitochondria
- aerobic glycolysis supplies membrane pump with ATP
what are the 2 uses of ATP in SM?
- phosphorylation of myosin light chain by MLCK
- dephosphorylation to separate head of myosin from actin
2 ways to reduce ATP usage in SM
- myosin isoform is different
2. latch mechanism
different myosin isoform
- slow ATPase activity
- slow cross bridge cycle
- any given contraction of SM uses fewer cross bridge cycles than skeletal muscle, so less ATP
latch mechanism
-how SM maintains contraction for low periods of time with very low ATP usage
latch mechanism steps
- initial depolarization/stimulus causes Ca levels in inc so we have lots of Ca-calmodulin and lots of myosin light chains are phosphorylated
- as contraction lasts longer (more time)
a. intracellular Ca levels dec
- due to inactivity of membrane pumps
b. decreased phosphorylation of myosin light chain
- MLCK activity dec as Ca/calmodulin dissociates
- inc in myosin light chain phosphatase activity
c. cross bridges that are attached can be dephosphorylated
d. continue to cycle which is now slower than before
- as they remain attached they generate tension
inhibition of skeletal muscle
- no direct inhibition of muscle itself
- if I want to relax muscle more, have to inhibit alpha motoneuron innervating the skeletal muscle and decrease number of AP
inhibition of SM
-can be directly inhibited by hormones and NTs
plasticity of SM
with time, passive tension decreases in SM even though the SM is stretched
- thick filaments are randomly arranged around cell not like in sarcomere
- when SM is stretched, the initial passive tension occurs b/c we have actin and myosin interacting with each other and they don’t stretch well
- with time, actin and myosin dissociate from one another which reduces tension
- “next” cross bridge cycle the myosin head that interacts with actin active site is on a different thick filament
