Lecture 33. Smooth muscle Flashcards
where is smooth muscle found?
bladder Blood vessels Gut Eye Airways
2 types of smooth muscle
Visceral (single-unit) smooth muscle
sheets of cells that are electrically coupled and act in unison i.e.
as one unit - often spontaneously active.
Found in most blood vessels and hollow
organs (respiratory, digestive, urinary
and reproductive tracts)
Multiunit smooth muscle
tissue made of discrete bundles of independent cells which are
densely innervated and contract only in response to its innervation (e.g., vas
deferens, iris, piloerectors)
arrangement of smooth muscle in the intestine
“single unit”
2 layers of smooth muscle:
longitudinal( outside)- moves food down the gut
circular(inside)- mixes food
smooth muscle cellular structure
-not striated
• No T-tubules – caveolae instead (act to increase surface area)
• Dense bodies act like z-lines to “anchor” actin to the sarcolemma
• In unitary smooth muscle cells gap junctions electrically connect the cells
together
• Intermediate filament is the cytoskeleton element
• Poorly developed SR( not associated with the cell membrane)
smooth muscle can contract more than skeletal(T/F)?
True
Due to the net-like arrangement of intermediate filaments and dense bodies
The actin filaments can slide over without interacting with other filaments
Can operate over large range of lengths (60 - 75%
shortening possible)
What junctions are in smooth muscle?
gap
What contractile proteins are in smooth muscle?
- myosin, actin
- tropomyosin BUT NO troponin
what causes the initiation AP in smooth muscle?
Electrical behavior is very complex but primarily due to voltage-gated
Ca2+ channels (relatively few Na+ channels)
The trigger for contraction is an increase in intracellular calcium. The Ca2+ entering through channels in the cell membrane is a very important source of calcium (i.e. less reliant on SR stores)
Can be neural, hormonal, or spontaneous
(myogenic)
How is calcium regulated in smooth muscle?
Ca2+ comes into the cell through:
• VDCC: Voltage-dependent Ca2+ channels (e.g. L-type Ca2+
channel)
• SOC: Store operated Ca2+ channel
• ROC: Receptor operated Ca2+ channel (often regulated
by DAG second messenger pathway)
How is calcium regulated in smooth muscle?
Ca2+ comes into the cell through:
• VDCC: Voltage-dependent Ca2+ channels (e.g. L-type Ca2+
channel)
• SOC: Store-operated Ca2+ channel
• ROC: Receptor operated Ca2+ channel (often regulated
by DAG second messenger pathway)
Agonist receptor- upregulates Ca2+ uptake through ROC
Ca2+ channels in SR:
-Hormones (e.g. angiotensin II) or neurotransmitters (e.g.
noradrenaline) acting on G-protein receptors to increase
IP3 levels, which act on IP3 mediated calcium release
channels in SR
- Calcium-induced calcium release via the RyR in the SR
- Ca2+/Mg2+ exchangers, SERCA pumps
On cell surface:
Ca2+ ATPase in surface membrane
Na+/Ca2+ exchangers
Outward rectifying the K+ channel important in regulating
membrane potential and thus voltage-gated channels- make the inside the cell more negative-> influence opening of V-gated channels
where does most of the calcium come from in smooth muscle?
the outside of the cell
initiation of contraction in smooth muscle
- Calcium ions (Ca2+) enter the cytosol from the ECF via voltage-dependent
or voltage-independent Ca2+ channels, or from the scant SR - Ca2+ binds to and activates calmodulin.
Note: in smooth muscle the regulatory protein is calmodulin, and the troponin complex is absent. - The activated calmodulin then activates(phosphorylated) myosin light chain kinase (MLCK). MLCK is an enzyme.
- MLCK activates the myosin by phosphorylating MLC, which in turn activates the myosin ATPases.
- Activated myosin forms cross bridges with actin of
the thin filaments and shortening begins in the usual
fashion.
What proteins regulate contraction in smooth muscle?
MYOSIN and NOT ACTIN
myosin binding site on actin is always available, need to energize the myosin for it to bind
why is smooth muscle contraction longer?
- Unlike AP MLCK is an enzyme, a longer process
- cross-bridge cycle is slower
- contracted all the time- eg blood vessels
Smooth muscle contraction is enzyme regulated –slow but efficient!
Smooth muscle relaxation process
Contraction ends when a myosin light chain phosphatase dephosphorylates the myosin light chain.
Ca-ATPase in cytoplasm membrane primary mechanism for reducing intracellular Ca++.
contraction vs relaxation stimulation
Increased MLCK activity (Ca2+ regulated) will favour contraction( activation of MLC)
Increased MLCP activity will favour relaxation(inactivation of MLC)
When intracellular Ca2+ drop MLCP activity will dominate
How can smooth muscle contraction be modulated?
- Changing Ca2+ levels
- Modulating MLCK and MLCP activity
Neurotransmitters- eg noradrenaline favor contraction-> increased MLCK activity
Hormones- most increase Ca2+-> increase MLCK activity
Environment- eg exercise-> decreases O2 levels in the muscle-> increase Ph-> vasodilation-> smooth muscle relaxation to increase blood flow
Histamine-> relaxation of smooth muscle
Adenosine-> waste product signal of a lot of metabolic activity-> vasodialtion-> relaxation
Nitric oxide- acts directly on MLCP-> relaxation
Innervation of smooth muscle
• Autonomic nerve fibers branch and form “diffuse junctions”
with underlying smooth muscle fibers.
• Varicosities in the terminal axons contain the neurotransmitter
• Neurotransmitter is secreted into the matrix coating and diffuses to the muscle cells. Affects many cells
Response to stretch in smooth muscle( length tension relationship)
When you stretch smooth muscle it will generally:
- Initially contract, effectively resisting the stretch (e.g. blood vessels trying to maintain blood flow constant)
- stretch-activated calcium channels. (left) - Over time slowly relaxes, adapting to the change in length (e.g. gut)
- via calcium-dependent K+ channels, hyperpolarizing the membrane potential
Response to stretch in smooth muscle( length tension relationship)
When you stretch smooth muscle it will generally:
- Initially contract, effectively resisting the stretch (e.g. blood vessels trying to maintain blood flow constant)
- stretch-activated calcium channels. -> contraction - Over time slowly relaxes, adapting to the change in length (e.g. gut)
- via calcium-dependent K+ channels, hyperpolarizing the membrane potential-> less Ca2+ comes in-> relaxation
