L12 Smooth Muscle Flashcards
Smooth muscle is
Unstriated
Involuntary
Autonomic
Where is smooth muscle found?
Walls of “hollow” organs and tubes
Smooth muscle functions
Maintain organ shape
Produces motility
Maintains pressure
Regulates internal flow
Autonomic nervous system, hormones, other local paracrine agents controls smooth muscle tone, contraction, and relaxation
Doesn’t necessarily require motor innervation!
How are smooth muscle cells nucleated?
Single nucleated
No T-tubules
Body tubes can have circumferential and longitudinal layers of muscle
What are type things about the smooth muscle cell structure
Less developed SR that is in contact with membrane
Lipids rafts for extracellular communication -caveolae (concave )
How is smooth muscle innervated?
ANS
Axon of postganlionic autonomic neuron has terminals that branch
Swellings that contain neurotransmitters are called varicosities ( not motor endplate!)
Two types of smooth muscle
Multi unit (neurogenic)
Single-unit (unitary) (myogenic)
Multi unit/ neurogenic smooth muscle
No gap junctions
High density of autonomic neurons
Every cell needs input of autonomic nervous system in order to function
Allows finer motor control
Eye, skin hair follicles, large blood vessels, small airways, vas deferens
Unitary /myogenic smooth muscle
Gap junctions (which permits coordianted contraction)
Low density autonomic innervation
Gap junctions
Cells linked by connexon tunnels
Connected anatomically
Connected electrically to form a functional syncytium
What muscle types are gap junctions found?
Single unit / unitary smooth muscle
Cardiac muscle
Types of filaments in smooth muscle
Thick myosin (longer than skeletal)
Thin actin
contain tropomyosin (present, not blocking)
NO TROPONIN
Actin/myosin gathered by dense bodies making them more diamond shaped than square
Arrangements of thick and thin filaments in smooth muscle cell
Relaxed- filaments not bound
Contracted- filaments interacting , allows sliding, muscle as a whole is reduced in size
Same as skeletal muscle
Uses ATP every cycle
How is cross bridge cycling regulation in smooth muscle?
Occurs on thick myosin head by light weight proteins attached to the myosin (myosin light chains)
Part where head bends have light chain portion
This area has high capacity phosphorylation site (not in skeletal muscle)
Kinase is enzyme that phosphorylates that portion - activates heads affinity for actin and ATPase
Calcium in smooth muscle may come from
SR or outside
What does Ca interact with when it comes out of the SR or outside in smooth muscle contraction?
Calmodulin
Ca-calmodulin complex
Complex activated myosin light chain kinase (MLCK) to phosphorylate myosin light chain
Turns on ATPase and myosin affinity for actin , crossbridge cycling and contraction occur
What happens when Ca drops in smooth muscle?
Not as much Ca-calmodulin complex
MLCK not activation
Myosin light chain phosphatase (MLCP) becomes activate and dephosphorylates myosin light chain
No ATPase activity , low affinity for actin , no cross bridge activity
What’s a main difference between crossbridge cycling mechanisms in skeletal and smooth muscle ?
Skeletal - physical reposition of troponin and tropomyosin
Smooth- series of biochemical events. Has an additional P on neck of myosin as well as ADP and Pi on head
How does Ca rise in smooth muscle?
Electro-mechanical coupling -Depolarization
Pharmaco-mechanical coupling- hormones or neurotransmitters
Electro-mechanical coupling/depolarization of smooth muscle
Action potential arrives, depolarizes cell
Opens voltage-gated Ca channels (outside to inside of cell) (if sufficient, will produces contraction)
If not - Ca induced Ca release from SR , Ca can act as second messenger to open rydianine receptors to allow more calcium in
Only in single unit smooth muscle (doesn’t require autonomic nerve to command it)
Pharmacy-mechanical coupling
Hormones/neurotransmitters require input from autonomic nervous system
Hormone/ neurotransmitter interact w/ receptor it may create second messenger IP3-gated Ca channels or open ligand-gated Ca channel
In both single unit and multi unit smooth muscle
What do IP3 gated Ca channels do?
Release Ca from SR through SERCA
Doesn’t go to Ca induced Ca release mechanism
What do Ligand gated Ca channels do?
Let Ca in
If not enough - can go to Ca induced Ca release from SR
Ca promotes actin-myosin interaction by stimulating myosin
Phosphorylation
A single excitation in smooth muscle does not cause
All cross bridges to switch on
(In contrast to skeletal muscle)
Ca conc increases, more cross bridges, greater tension
What are the ATPases and exchangers in smooth muscle?
SERCA -primary active (in cell)
Na/K ATPase- primary active (on membrane)
Sacrolemmal Na/Ca exchanger - secondary active (on membrane)
Sacrcolemmal Ca ATPase -primary active (on membrane)
To decrease contractile force , decrease conc of intracellular Ca
How do they correlate to smooth muscle relaxation?
Na/K ATPase creates ion gradient
SERCA reduces cytosolic Ca conc by returning Ca into SR
Sarcolemma Na/Ca exchanger pumps Ca outside cell through Na/K ATPases Na gradient
Sarcolemma Ca ATPase pumps Ca out actively
This allows phosphatase to be more active in the cell and promotes relaxation
How’s smooth muscle tone regulated?
Intercellular amount of Ca
MLCK to MLCP ratio
Smooth muscle drugs
Calcium antagonists
cAMP
cGMP (stimulus and inhibitors)
Calcium antagonists directly
Vasodilators
Block voltage gated Ca channels DIRECTLY, can’t get Ca-calodulim complex, MLCK not recruited, no possibility of crossbridge formation
RELAXATION
Calcium antagonists indirectly
Potassium channel openers
Vasodilators
Opening of channel hyperpolarizes membrane will reduce ability to open voltage gated Ca channels
Reduces Ca-calmodulin complex and MLCK
RELAXATION
cAMP smooth muscle drug
RELAXES smooth muscle by inhibiting MLCK even with Ca present
Beta2 adrenergic receptor agonists ,
when activated adrenergic receptor procures cAMP and blocks MLCK
cGMP smooth muscle drug
RELAXES smooth muscle by decrease Ca and activating MLCP (myosin dephosphorylation)
Nitric oxide Stimulates cGMP production
phosphodiesterase- inhibit cGMP degradation which increases cGMP and activates MLCP
Nitrates and phosphodiesterase inhibitors
Reduces Ca flow from Ca voltage gated channels
Enhances MLCP
