smooth muscles Flashcards
What is smooth muscle?
why smooth?
Why ‘Smooth’?
Does not contain rigid cellular structures coupling stimulation to contraction – no striations as with skeletal and cardiac muscles
Where do you find smooth muscle?
2 examples
what does it do there?
Found in “walls” of tubular organs
e.g. blood vessels, GI tract, airways, uterus, bladder, eye
e.g. Blood vessels:
Contraction or relaxation of circular smooth muscle cells -> changes in diameter -> change blood flow
e.g. GI tract:
Contraction or relaxation of circular and longitudinal smooth muscle -> change movement of gut (peristalsis)
Clinical importance
Regulation of smooth muscle is an important goal in treating disease e.g. Hypertension, urinary incontinence, COPD, IBS
Characteristics of Smooth Muscle
speed of contraction?
strength?
innervated by?
myogenic?
Slow, sustained, graded contraction
Relatively weak contraction (vs. skeletal/cardiac muscle)
Innervated by Autonomic Nervous System (ANS)
Can have spontaneous contractions (myogenic)
Excitable cells - produce action potentials like skeletal muscle & cardiac muscle
Transmitters released from post-ganglionic autonomic nerves onto smooth muscle cells
neurotransmitters that affect smooth muscles? released from where?
Transmitters released from post-ganglionic autonomic nerves onto smooth muscle cells are:
Acetylcholine (Ach) – parasympathetic nerves
Noradrenaline (NA) – sympathetic nerves
Nitric oxide (NO) - released from NANC (non-NA-non-Ach) nerves Adrenaline - from adrenal medulla
How does Smooth muscle contract?
initiated by?
how does it occur? (2)
As with striated muscle (skeletal and cardiac),
Smooth muscle contraction is initiated by an increase in cytosolic Ca2+ concentration ([Ca2+]i)
Increase in [Ca2+]i occurs via:
Increase in Ca2+ influx from the extracellular medium
Release of Ca2+ from internal Ca2+ stores
(sarcoplasmic reticulum)
Smooth muscle uses
Ca2+-Calmodulin-Myosin light chain kinase system
produce contraction
where does ca2+ bind?
what does this activate?
what does this phosphorylate?
Intracellular Ca2+ concentration increases when Ca2+ enters cell and is released from SR
Ca2+ binds to calmodulin (CaM)
Ca-calmodulin activates the enzyme, myosin light chain kinase (MLCK)
MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity
Active myosin crossbridges slide along actin hence sliding filament theory + contraction
Increase in Ca2+ influx
what must open? how will these open?
Stimulation of G-protein coupled receptors (Gq family)
e.g. Ach on Mus (M3) in airways, NA on α1 in blood vessels
Gq- PLC – PIP2 into IP3 and DAG
Action on ion channels
Depolarisation
e.g. From resting membrane potential of -60mV to -30mV
Activation of Voltage-gated Ca channels (VGCCs) – threshold -40 mV
Produces Ca2+ influx
Release of Ca2+ from internal Ca2+ stores
where is it released from? what acts on this to release it?
difference from cardiac and skeletal?
Stimulation of G-protein-coupled Receptors (Gq family)
Generation of IP3 IP3 receptor on SR Release of Ca from SR down concentration gradient High Ca2+ in SR (500 µM) Low Ca2+ in cytosol (100 nM)
Remember : Smooth muscle contraction uses IP3 receptors not ryanodine receptors (RyR, cardiac/skeletal muscle contraction)
In absence of a rise in cytosolic Ca2+
Myosin light chain phosphatase produces relaxation
if no ca2+ what dominates? effect of this?
what does this lead to?
If no Ca2+ availabale, MLC-phosphatase will dominate and hence any phosphorylated myosin light chain will become dephosphorylated myosin light chain
No rise in Ca2+ :
No Ca-CaM
No MLCK activation
MLCP activity dominant
Relaxation
What causes relaxation of smooth muscle cells? Decrease in [Ca2+]i
3 things that decrease ca2+
effect of this? leading to?
[Ca2+]i decreases:
Hyperpolarisation caused by K+ channel opening – close VGCCs
Ca2+ uptake into SR - Ca2+-ATPase
Extrusion of Ca2+ from cell - Ca2+-ATPase Na-Ca exchanger
Decrease in [Ca2+ ]i reduces MLCK activity
Balance in favour of MLCP
Less MLC-P
Less actin-myosin interactions
Neurotransmission to smooth muscle – Autonomic nerves
Excitatory Neurotransmission
why is it dealyed and slow sustained contraction?
why must NA/Ach bind?
leads to? effect of this?
repolarisation starts when? effect of this?
Delayed, slow, sustained contraction due to time taken to switch on and off Ca2+ stimulated contractile events
1) Release of excitatory transmitter (Ach, NA) binds to receptor -> junctional depolarising potential
(2) Threshold for VGCCs -> open VGCCs -> more Ca2+ influx -> muscle contraction
Important : VGCCs cause upstroke of action potential
(3) Open K+ channels -> repolarisation -> close VGCCs ->
less Ca2+ influx -> muscle relaxation
Neurotransmission to smooth muscle
Inhibitory Neurotransmission
example of an inhibitory mediator
what does it do?
Relaxation
Showing that smooth muscle has resting tone
Inhibitory mediator such as nitric oxide hyperpolarises smooth muscle by opening K+ channels (e.g. corpus cavernosa)
Close VGCCs -> less [Ca2+]i -> Relaxation
Comparison of pathways involved in
skeletal, cardiac, and smooth muscle contraction
nerves? release? pathways? ryr and vgcc? if no ryr?
Skeletal (Striated, voluntary)
Motor nerves release Ach at NMJ activating Nicotinic ligand-gated
Physical-interaction Between VGCC and RyR coupled to Ca release
Troponin
Cardiac (Striated, involuntary) No nerve input required Modulated by B1-Gs pathway VGCC-mediated - Ca influx coupled to RyR-mediated Ca release ‘’Ca induced Ca release’’ Troponin
Smooth (involuntary) Release of NT from ANS e.g. Ach, NA activates Gq-receptors VGCC-mediated Ca influx and IP3-mediated Ca release Calmodulin/ Myosin light chain kinase
