GI Smooth Muscle Flashcards
What’s in sm. m
Thick filaments,
Thin filaments,
SR (less developed than sk. m) that contains Ca2+
smooth muscle must be able to
contract and maintain that contraction for a long period of time
must be ENERGY EFFICIENT - use little ATP
maintain shape of organ, but allow for distension
continue to generate active tension even when stretched
Thin filaments in sm. m
actin anchored to dense bodies 2X as in sk.m tropomyosin - but doesnt cover active site NO TROPONIN
Thick filaments in sm. m
1/4 of that found in sk. m
different isoform
contains kinase, and phosphatase
slower contraction than sk. m.
can sm m be directly inhibited
yes
Intrinsic innervation of sm. m
gut, trachea, (enteric plexus)
neurons (sensory and motor)
independent of CNS and PNS
Extrinsic innervation of sm. m
ANS, allows CNS to control viscera
Ach
excites some smooth m (gut)
may inhibit other (cause relaxation)
Norepi or epi
causes contraction of vascular sm. m
inhibits gut sm. m
NO
vasodilator and relaxor
major inhibitory influence on sm. m
acts via cGMP mechanism
Sm. m neuromuscular neuromuscular contact
no motor end plate, synapses en passante
varicosities: swellings in axon. NT is released from the varicosity, then diffuses to find receptors on sm. m
Sm. m. neurotransmitter receptors
muscarinic cholinergic
adrenergic alpha and beta
NO is extremely lipid soluble, doesnt require receptor, diffuses through and has action on cGMP system
Hormones that can elicit sm. m contraction
epi
CCK
gastrin, motilin
Activation of GI sm.m by paracrine agents
EDRF= endothelial derived relaxinf factor, now known as NO
inhibits smooth muscle
other forms of sm. m activation
can be activated by stretch. some of the sm. m in the vasculature can be activated this way
Calcium regulation in Sm. m contraction
VERY dependent on Ca2+, even more so than cardiac m
comes from extracellular stores or SR
regulated seperately and play different roles in contraction
AP always necessary for sm. m contraction
NO
Release of Ca2+ from SR
Epi or n-epi binds –> Gqprotein –>increase IP3 and DAG= Ca released from Sr
PKC is activated as part of this process
BECAUSE OF THIS, SM. M CAN BE ACTIVATED TO CONTRACT IN ABSENCE OF AP
Extracellular Ca2+
particular importantance in sm. m. does somewhat rely on AP
voltage gated Ca-ch opens with depol
ligang gated Ca-ch opens with binding of ligand
IMPORTANT sustained contraction of sm. m require Ca2+ from extracellular stores,
longer contration, more it relies on extracelluar Ca
Sm. m at rest
tropomyosin not covering active site. we have no troponin
addition of 2 myosin light chains, = decreased affinity of myosin head for actin sites
at rest, the MYOSIN LIGHT CHAIN is dephosphorylated and myosin isnt particularly interested in binding to actin active site. no need to cover with tropomyosin.
still have MYOSIN HEAD bound to ATP and Pi
Smooth Muscle Contraction
Step 1= increase in intracellular calcium
Step 2= calmodulin binds with Ca. = activates the calmodulin
Step 3= calmodulin activates MLCK, which takes an ATP, hydrolyzes it to make ADP and Pi
Step 4= MLCK phosphorylates the light chain
Step 5= myosin cross bridge can begin cycle
now we get myosin binding actin, Pi dissociates and then ADP dissociates= power stroke. these 2 filaments are stuck until ATP comes in and binds the myosin head. when it does that, we see the release of the myosin head from the active site as we hydrolyze atp to adp and pi.
Where do the two distinct Pi work in sm. m contraction?
one at they myosin head, the other at the myosin light chain
Sm. m. Relaxation
occurs when we remove Ca from the calmodulin, inactivate the MLCK, and activate the phosphatase.
inactivating MLCK will activate a phophatase, which removes the Pi from the myosin light chain and allow relaxation
The Latch mechanism
the Pi can be removed from the myosin light chain at any point in the cycle, the cycle will continue but VERY slowly, and a new cycle can not be started
any activated cross bridges are still generating tension. but not using energy.
WITHOUT ATP, AND WITH A DEPHOS MYOSIN LIGHT CHAIN
INCREASES TENSION AND DECREASES ATP USAGE
Length- Tension relationship in sm. m
stretch muscle, passive tension increases a little, but actin and myosin rearrange and passive tension dissapates
the random arrangement of actin - allows us to disappate passive tension and to maintain active tension over a wider range of lengths.
Sm. m plasticity
capable of dedifferentiation and differentiation
in damage, can become a fibroblast to secrete collagen for repairs
once damage is repaired, differentiates back into sm. m of blood vessel
