Week 15: Physiology of Smooth muscle Flashcards
what muscle types are voluntary?
skeletal
What muscle types are striated?
skeletal and cardiac
What muscles types are part of the autonomic innervatio?
smooth and cardiac
What are striations due to?
organisation of a contractile proteins in individual muscle fibres
actin and myosin proteins= orderly
What are the key features of skeletal muscle?
Individual muscle fibres are large, elongated, cylindrical and possess multiple nuclei
What are the key features of cardiac muscle?
Individual muscle fibres are large, cylindrical and possess multiple nuclei
What are the key features of smooth muscle?
Individual muscle fibres are relatively small, spindle shaped, and possess one nucleus
What neurones are involved in skeletal muscle?
alpha and gamma neurone
What fibres are involved in cardiac and smooth muscle?
sympathetic and parasympathetic postganglioic fibres
Where is smooth muscle mostly found?
walls of hollow organs and tubes
What does smooth muscle mediate?
propulsive movements and exerting pressure
What are the 2 classes of smooth muscle?
phasic & tonic
What is phasic smooth muscle?
muscle exhibits rhythmic or intermittent activity
What is tonic smooth muscle?
muscle that is continuously active
What is an example of a phasic smooth muscle that is phasically active?
phasically active
stomach intestines underlies peristalsis
What is an example of a tonic smooth muscle usually in contracted state?
normally contracted
sphincter
prevent faeses from rectum to anal canal
What is an example of a phasic muscle normally in the relaxed state?
normally relaxed
oesophagus, urinary bladder
What is an example of tonic smooth muscle?
normally partially contracted
blood vessels, airways
What can smooth muscles also be classified as?
- Single unit (connected by gap junctions)
- Multiunit ( muscle cells are not electrically coupled, activity in one cell does. not results in activity in another)
What does the single unit smooth muscle stimulate?
wave contraction across a muscle sheet
only stimulated by one type of neurone
What does the multiunit smooth muscle stimulate?
individual muscle fibres
What allows finer control of smooth muscle, multiunit or single unit?
multiunit
stimulated by parasympathetic and sympathetic post ganglionic neurones
What are the muscles which a single unit smooth muscle will stimulate?
stomach, intestines, urinary bladder, airway smooth muscle
What are the muscles which a multiunit smooth muscle will stimulate?
iris, vas deferens
What type of filament does smooth muscle contain?
myosin, actin & intermediate
What proteins form most of the intermediate filament in smooth muscle?
desmin and vimentin
What does the actin of smooth muscle lack?
contains tropomyosin but lacking troponin
Where does Ca2+ bind
What structure is important in maintaining the shape of the cell?
intermediate filaments
What direction do actin filaments run?
parallel to the long axis of the cell
Why is the smooth muscle unorderly and unstriated?
filaments do not form myofibrils
no sarcomere patternNo Z line
With no Z line in. smooth muscle, where do actin filaments bind to?
attach to dense bodies in the cytoplasm and dense bands at the inner surface of the plasmalemma
What contains more actin skeletal or smooth?
smooth
How does contraction occur in smooth musc;e?
very similar to skeletal (cross bridge + Ca2+ dependent)
Apart from the contraction is over dense band to dense body to the other dense band
What does Ca2+ bind to?
calmodulin in the cytoplasm
What is the change in Ca2+ conc. from a maximal contraction to occur?
100nM to 1 microM
up 10 fold
what does Ca2+-calmodulin activate?
MLCK enzyme
What does active MLK permit?
the transfer of organic phosphate to the myosin head
What is required for actin to myosin binding?
ATP
Why is additional ATP required in contraction?
ATP is required for cross bridge cycling to continue via hydrolysis
What is calmodulin? Where is it found in a cell?
multifunctional Ca2+ binding protein
present in the cytoplasm of all eukaryotic cells
What happens when 2 or more Ca2+ molecules bind to calmodulin?
undergoes a large confo change
the strand under the 2 lobes to become an alpha helix
Where does Ca2+ bind to on calmodulin?
2 Ca2+ binds to EF hand motifs
4Ca2+ per calmodulin
called CaM
What can CaM bind to?
vast range of kinase peptides
e.g. CaM kinase
What does CaM activate?
MLCK
Is calcium calmodulin an enzyme?
NO
What is activated in smooth muscle contraction?
myosin
What can smooth muscle contraction be called?
myosin based contraction
How does contraction occur in smooth muscle?
phosphorylation of the regulatory myosin light chain (MLC) in the presence of elevated intracellular Ca2+ (and ATP)
How does relaxation occur of smooth muscle?
dephosphorylation of MLC by myosin phosphatase which has constitutive activity, but is also regulated
What chain in phosphorylated in myosin?
light chain
What is the differnece between MLCK and MP?
MLCK phosphorylates MLC
MP de-phosphorylates MLC
What autonomic innervation do arteries primarily receive?
sympathetic (NA) adrenoR
What autonomic innervation do other tissue receive?
symp and para innervation(ACh, muscarinic)
What autonomic innervation occurs in the G.I tract?
enteric/ANS
What tissue have no autonomic innervation?
uterus
Where does chemical transmission between autonomic neurones and smooth muscle take place? The junction between postganglionic fibre
neuroeffector junctions
What are varicosities?
where the transmitter is released from. many of them along nerve fibre
What factors can increase/decrease smooth muscle activity?
- Hormones
- Autonomic neurotransmitter
- Pacemaker activity of smooth muscle itself
- Many therapeutically important drugs
What can increase [Ca2+]?
- Ca2+ influx from the extracellular fluid by cell-surface voltage-activated Ca2+ channels opened by membrane depolarisation
- Release of Ca2+ from intracellular stores, typically as a result of the activation of cell surface G protein-coupled receptors (GPCRs)
What is pharmacomechanical coupling?
-Processes by which an agent causes a change in smooth muscle tone without a change in membrane potential
What does a secondary messenger do in pharmacomechanical coupling?
-That either contract, or relax, the muscle
What are the important secondary messengers in pharmacomechanical coupling?
- Inositol trisphosphate (IP3) causing contraction
- (cGMP) and cyclic adenosine monophosphate (cAMP), both causing relaxation
What processes can E-C coupling be described as?
Pharmacomechanical coupling Electromechanical coupling (in reality the 2 overlap to some extent)
What us electromechanical coupling?
opening of plasma membrane voltage-activated L-type Ca2+ channels in response to depolarization with, or without, action potential generation
In pharmacomechanical coupling in smooth muscle how is Ca2+ released into the SR?
IP3 – generated by activation of PLC opens IP3 receptors in the SR membrane releasing Ca2+
In electromechanical coupling what does the released Ca2+ bind to?
-Opening of Ca2+-activated chloride channels (CaCC)
-Ca2+ in to cell causing depolarisation
OR// binds to CaM= contraction
What does DAG bind to and activate/ inhibit?
Inhibit K+ channel directly or activate PKC to then inhibit the channel (keep positive charge in)
-Na/Ca channel, Ca2+ in to cell
What does the depolarisation in electromechanical coupling lead to?
Opens voltage-activated L-type Ca2+ channels, further increasing [Ca2+]i and contraction (4)
What 2 mechanisms decreases Ca2+ levels and cause relaxation?
pumped back into SR via a Ca2+ ATPase (SERCA)
Pumped out of cell via Na/Ca exchanger or Ca2+ ATPase
