Physiology Of Smooth Muscle Flashcards
Is the sarcoplasmic reticulum found in skeletal muscle or smooth muscle?
Both but is less developed in smooth muscle
The release of Ca from the SR in smooth muscle involves what receptor?
GPCR which produces IP3 and DAG (Gq/ii)
IP3 stimulates Ca release from the SR
Which types of channels allow Ca entry into smooth muscle cells?
Voltage gated (open with depolarization) and ligand gated Ca channels (open with binding of ligands)
Why does sustained contraction of smooth muscle require Ca from extracellular sources?
There is not enough Ca in the SR to maintain contraction for a long period of time which is important because most of the smooth muscle in the body is in the contracted state
What are the steps for smooth muscle contraction?
- Increase intracellular Ca concentration
- Ca binds to calmodulin
- Calmodulin activates MLCK
- MLCK phosphorylates one of the two myosin light chains
- Myosin cross bridge cycle can begin
- Myosin binds to actin causing the myosin head to lose ADP + Pi causing a conformational change in myosin and creates the power stroke
Why is tropomyosin not needed in smooth muscle?
Myosin has a low affinity for actin which is increased by the phosphorylation of its light chain by MLCK to allow for binding
What are the two distinct inorganic phosphates that are involved with myosin during smooth muscle contraction?
One on the light chain
The other at the myosin head associated with the ATPase
At what point can myosin and actin dissociate from each other during smooth muscle contraction?
Not until ATP binds to the myosin head which decreases myosin head affinity for actin causing them to dissociate
What creates energy to move the myosin back into the “ready” position to allow for the next cross bridge cycle in smooth muscle to begin?
The energy created by ATP being hydrolyzed into ADP + Pi
What causes relaxation of smooth muscle of contraction?
Pump Ca out of the cell —> Ca dissociates from calmodulin —> MLCK inactivated —> MLCP activated which removes inorganic phosphate from the myosin light chain allowing for relaxation
Is an AP required for skeletal muscle contraction?
Yes
Is an AP required for smooth muscle contraction?
No -> hormones can illicit smooth muscle contraction
What is the role of Ca during skeletal muscle contraction?
4 Ca bind to troponin C and a conformational change occurs in troponin
What is the role of Ca in smooth muscle contraction and what is the effect?
Ca binds to calmodulin and causes activation of MLCK
What mechanism allows actin and myosin binding in skeletal muscle?
Tropomyosin is removed from active sites
What mechanism allows actin and myosin binding in smooth muscle?
MLCK phosphorylates myosin light chain
Describe the cross bridge cycle in skeletal and smooth muscle
Cross bridge cycle is the same in both
What causes skeletal muscle relaxation?
Removal of Ca from troponin reverses conformational change to cover active sites and prevents contraction
What are the two main mechanism that allow smooth muscle to overall consume less ATP even though it uses 2 ATP/cycle?
Slower myosin/ATPase isoform
Latch mechanism
How does a slower myosin/ATPase isoform allow smooth muscle to consume less ATP?
Fewer cross bridges per unit time which reduces its overall ATP use
Describe the latch mechanism
The Pi on the myosin light chain can be removed from any point in the cross bridge cycle
Cycle will still go through the power stroke after Pi removal but it stops afterwards with myosin and actin bound to each other
This causes a delay in their dissociation which maintains muscle tension and reduces overall use of ATP
How many ATP are used for skeletal muscle contraction?
1 ATP/cycle to separate actin and myosin
What ion ATPases are present in skeletal muscle?
Na/K, Ca (SR) and other membrane bound ATPases
Smooth muscle has same ones but has a SR and membrane Ca ATPase
What is intrinsic innervation of smooth muscle?
Present in select smooth muscle in the gut and trachea
Includes both sensory and motor neurons
Independent of the CNS and PNS
What is extrinsic innervation of smooth muscle?
Present in almost all smooth muscle
Involves the ANS and allows the CNS to control viscera
How is smooth muscle contraction controlled neurally?
Through NTs like ACh, NE and NO
How does ACh control smooth muscle contraction?
Excites some smooth muscle (ex. In the gut)
May inhibit others and cause relaxation
Binds to muscarinic cholinergic receptors
How does NE control smooth muscle contraction?
Causes contraction of vascular smooth muscle
Inhibits gut and bronchial smooth muscle
Binds to alpha or beta adrenergic receptors
How does NO control smooth muscle contraction?
Major inhibitory influence on smooth muscle
Acts via a cGMP mechanism
Current believed that NO doesnt require a membrane bound receptor bc it is extremely lipid soluble so it diffuses through the cell membrane to influence the cGMP system
What is a major difference between smooth and skeletal muscle?
Smooth muscle can be directly inhibited (caused to relax)
What are varicosities?
Swellings in an axon that function as the presynaptic terminal
NTs are released from them
How is smooth muscle controlled via hormones?
Some examples of hormones which can elicit smooth muscle contraction include epinephrine (from adrenal medulla)
As well as CCK, oxytocin and angiotensin
How can smooth muscles be activated by paracrine agents?
Endothelial cells secrete EDRF (endothelium derived relaxing factor) which is now known to be NO
Causes same effect of relaxation of smooth muscle vasculature resulting in vasodilation
What are some other forms of controlling smooth muscle contraction?
Can be activated by stretch
Occurs in the vasculature
Can be initiated by damage to the blood vessel wall which is known as a myogenic response
How can contraction of smooth muscle be controlled?
Neurally, through hormones, paracrine agents as well as stretch
What is skeletal muscle innervated by?
Alpha motor neurons
What is smooth muscle innervated by?
ANS or intrinsic innervation
What NT is used for skeletal muscle contraction?
ACh
What is the transmission specialization in skeletal muscle?
NMJ
Presynaptic terminal and specialized motor end plate
What are the transmission specializations for smooth muscle?
Varicosities and receptors in multiple locations
What NT receptors are present on skeletal muscle?
Nicotinic cholinergic
