Transcript Visceral Muscle - Washington State University

Visceral Muscle
How is the gut organized anatomically?
The two major gut plexi
contain motor neurons,
interneurons and
sensory neurons. This
diagram doesn’t show
it, but many of the
chemoreceptors are
enteroendocrine cells
(modified epithelial
cells). There are
approximately as many
neurons in the gut as in
the CNS
What do smooth muscle cells look like?
Organization of the contractile machinery in
smooth muscle
Dense body
made of alpha
actinin
attaches actin
to actin
Dense plaque
attaches actin
to sarcolemma
In smooth muscle Ca2+ controls contraction
through a soluble Ca2+ binding protein and a
soluble kinase
• Contractile machinery of all muscle consists of
actin (thin) filaments to which force is applied by
myosin (thick) filaments which project heads
(crossbridges).
• Control is exercised at the thin filaments in
striated muscle (skeletal and cardiac), but
primarily at the thick filaments in smooth muscle.
• The calcium-binding molecule in smooth muscle
is a soluble protein, calmodulin.
• The protein that controls the activity of myosin
heads is myosin light chain kinase (MLCK)
Ca2+ can come from external or
internal sources
• External: entry across the cell surface
through L Ca2+ channels – this is an
electromechanical process
• Internal: release from internal stores
(endoplasmic reticulum) caused by 2nd
message – this is a pharmacomechanical
process.
The sequence of events in thick
filament control in smooth muscle
• Ca++ binds to calmodulin
• Ca++-calmodulin binds to MLCK
• MLCK-CM-Ca++ phosphorylates myosin
regulatory light chain
• Head associates with actin and begins to
cycle
• Cycling continues until Pi is removed by
myosin light chain phosphatase (MLCP)
Relaxation requires both removal of
Ca2+ and dephosphorylation of MLC
• Ca2+ is removed by Ca2+ pumps in ER and
cell surface.
• Dephosphorylation of MLC is by myosin
light chain phosphatase.
Acetylcholine turns on intestinal smooth
muscle through a 2-pronged 2nd message
• Muscarinic receptor is coupled to Phospholipase
C (PLC) attached to cytoplasmic side of plasma
membrane.
• PLC converts phosphatidylinositol bisphosphate
(a membrane phospholipid) into
– diacylglycerol (DAG) which diffuses in PM, closes
‘rest’ K+ channels and thus activates voltage-sensitive
L Ca2+ channels
– phosphoinositol trisphosphate (IP3) which diffuses
in cytoplasm and releases Ca2+ from endoplasmic
reticulum
Phospholipase C
splits off the
“tails” of the
phospholipid as
DAG, and adds a
phosphate to the
“head” to form IP3
Epinephrine turns off intestinal smooth
muscle through a cAMP 2nd message
• Binding of Epi to Beta2 receptor initiates
cAMP 2nd message
• cAMP activates Protein Kinase A (PKA)
• PKA phosphorylates MLCK
• Phosphorylated MLCK cannot be
activated by Ca2+-calmodulin
Norepinephrine
Beta adrenergic
receptor
cAMP
PKA
MLCK-P
(inactive)
Important points
• In smooth muscle, force modulation is the
result of changes in the number of cycling
myosin heads – this can be achieved in
several different ways
• Smooth muscle is adapted to deliver force
over a wide range of working lengths