Download Striated muscle contraction in skeletal/cardiac muscle

Striated muscle contraction in skeletal/cardiac muscle.
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Skeletal muscle 50-100 um thick with 40 um width fibres. Peripheral nucleus.
Cardiac muscle 20 um thick and 120 um long.
o Muscle -> fibre -> myofibril -> sarcomere.
Sarcomere
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Lattice of thick filament protein (M) and thin filament protein (A)
1 thick filament surrounded by 6 actin filaments
Interaction of filaments -> contraction.
Z lines (actin), I line (actin), A lines (myosin)
Contraction from 2 um length to ~ 1.6 um length
500 sarcomeres in 1 mm muscle
Contractile proteins
 Contractile myosin and actin
 Regulatory proteins on thin filament: tropomyosin and troponin I, C and T.
 Accessory proteins – titin and nebulin
 Myosin S1 heads clustered at filament ends, tails in the centre. Total of
250 molecules per thick filament.
Contraction
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Z lines move towards each other, shortening sarcomere. I lines disappear
and A lines stay same length-wise.
Thin filament sliding over thick filament -> cross bridging -> movement
towards centre Z line.
Cross bridge formation
 At rest, actin bound to troponin I, anchoring tropomyosin and troponin T.
Upon Ca influx into cytoplasm, Ca binds troponin C which then binds
troponin I, dislodging actin and exposing it to interaction with myosin
where it binds to actin binding sites on the S1 head.
 ATP-dependent reaction. S1 contains ATP binding pockets where it is
hydrolysed to enable cross bridging.
Skeletal muscle excitation
 Motoneuron motor end plate forms NMJ at muscle sarcolemma. End plate
potential causes ACh release into cleft.
 ACh binds to receptors on sarcolemma, generating AP which propagates
along membrane and enters t- tubule – a transverse tubular system that
allows AP to be propagated from tubule to tubule.
 AP reaches SR which causes Ca release from Ryanidine receptors on
terminal cisternae.
 Ca binds troponin C, unblocking tropomyosin and thence actin. Cross
bridging ensues.
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Upon cease of AP, Ca dislodges from troponin C, restoring tropomyosin
and actin anchorage which causes relaxation.
Ca returns to the SR via the SERCA Ca membrane pump.
Length-tension relationship
 At same [Ca] a shorter myofibril produces a bigger force of contraction
than the longer one
 Increased length before contraction means less filament overlap.
 Decreased length before contraction means there is overlap already so less
overlap formed and less force of contraction.
 Optimal myofibril length produces steep phase of increase of tension.
 Cardiac muscle has steeper ascending phase due to higher troponin C
affinity for Ca and thus higher sensitivity of cardiac muscle for Ca. During
excitation there is 1 um [Ca] and 0.5 uM stimulates a rise in tension
followed by a fall. A long sarcomere provides feedback to troponin C
to increase affinity for Ca.
 During skeletal muscle excitation 10 uM of Ca in cytosol with 1-2 uM
stimulating rise in tension. No sarcomere feedback to troponin C on
excess of Ca.
Ca concentration-tension relationship
 Sigmoidal relationship: an increase in Ca causes a steep increase in
tension (steeper in cardiac muscle for sufficient force of contracton)
 Optimal concentration enables highest tension above which it won’t
increase on further Ca increase.
Tetanic summation
 A single AP causes a single contraction which causes a single heart beat –
important for cardiac myocyte function. No tetanic summation as heart
muscle has to relax during diastole.
 Skeletal muscle titanic summation when there is continuous excitation. A
high frequency of stimuli causes continuous Ca influx into cytosol for
troponin C binding. As a result a greater force of contraction achieved.
Cardiac muscle twitch amplitude
 A relationship between ventricular volume and pressure – bell shaped.
 Following diastole, increased VR increases ventricular volume which
stretches cardiac muscle and increases the twitch amplitude causing a
greater force of contraction and thus a greater stroke volume.
Smooth muscle contraction
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Spindle-shaped cells 100um thick with gap junctions and desmosomes joining.
No visible pattern of striations as SR and filaments are irregularly arranged to
allow for greater contraction.
Cells surrounded by elastic elements.
Smooth muscle found in vascular, respiratory, GI and uretogential tract walls.
Contractile proteins
 Dense body of actin on cell surface – two bodies form mechanical junction.
 Intermediate (actin) filaments connect dense bodies to myosin obliquely to
the cell axis causing globular appearance on contraction (when filaments
pull dense body and myosin towards each other)
 No regulatory proteins on thin filament but regulation of thick filament.
Contraction
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Ca derived from SR and from extracellular fluid via activation of L-type
Ca channels by membrane depolarization.
4 Ca ions bind one calmodulin (CaM) protein to form a complex which
activates MLCK by displacing the auto-inhibitory region of the kinase
MLCK phosphorylates myosin S1 head light chains, increasing myosin’s
ATP-ase activity to hydrolyse ATP
As a result, increase actin binding and cross bridge cycling causing an
increase in tension
Phosphatise removes PO32- group from the light chain, resulting in
relaxation.
ATP required for myosin light chain phosphorylation and during cross
briding with actin, resulting in a net loss of 2 ATP molecules.
Length-tension relationship
 less steep and smaller in smooth muscle but force of contraction
increased at shorter sarcomere lengths.
Flagella/cilia
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Motile unit is axoneme
No myosin or actin
C/S of an axoneme shows 9 + 2 arrangement of microtubules
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Nexin joins outer microtubules to eachother
Spoke protein joins outer microtubules to inner pair
Dynein enables microtubule sliding relative to each other in a cross bridge
fashion.
Proteins
Microtubule
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Doublet structure
Each tubule a heterodimer of alpha and beta tubulin of which 13
protofilaments are comprised and 3 of them shared by both tubules.
Bending
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Combination of motile sections with those of fixed geometry
100nM-10uM Ca concentrations next to microtubules to modulate their
activity.