Transcript Chapter 49 The Neuromuscular Junction and Muscle Contraction

Chapter 49
• The Neuromuscular Junction and
Muscle Contraction
1
Propagation of an action potential along an axon.
In myelinated nerves, clusters of sodium ion channels can
be millimeters apart from each other.
2
Chemical Synapse
NT is released by exocytosis
Post-release of the NT
-it can be destroyed by enzymes
(acetylcholinesterase)
-taken up by the nerve terminal
that released it (reuptake)
-taken up by surrounding glial
cells.
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Transmitter-gated ion channels
1) Concentrated in the region of
the synapse.
2) Open momentarily allowing
brief permeability to the ion.
3) The more NT released the
longer the gates are opened.
4) The resulting action potential
can only be triggered only if
the membrane potential
increases enough to open a
sufficient number of voltagegated cation channels.
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Neuromuscular
Junction in a Frog
-single axon on a
skeletal muscle cell.
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The Acetylcholine Receptors at the Neuromuscular
Junction Are Transmitter-gated Cation Channels.
• Between a motor neuron and a skeletal muscle
• Ach receptor gene was the first ion channel gene to be cloned and
sequenced.
• Only ligand-gated channel whose 3-D structure has been
determined.
• Receptor is made of 5 transmembrane polypeptides
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Encoded by 4 separated genes
The 4 genes are very similar in sequence implying they evolved from a single
ancestral gene.
2 Ach molecules bind to the complex and opens the channel.
Acetylcholinesterase.
If Ach persists for too long as a result of excessive nerve stimulation, the
channel inactivates.
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Three conformations of the Ach receptor
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Structural Model for the Ach Receptor
Closed State: blocked by hydrophobic side chains of 5 leucines
Negatively charged side chains at the ends of the pore ensure that only
cations (mainly sodium, potassium with some calcium) will pass
through the channel.
Influx of sodium ions leads to membrane depolarization and muscle
contraction.
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NM Transmission Involves 5 Different Sets of Ion Channels.
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Molecular Motors
• Motor Proteins
• Use energy from repeated ATP hydrolysis to move.
• Lots of different motor proteins in eukaryotic cells.
• They carry “cargo” (organelles), or they cause cytoskeleton
filaments to slide against each other such as in muscle contraction,
ciliary beating and cell division.
• Basic Makeup
• Head Region or motor domain: binds and hydrolyzes ATP.
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Myosin II: 2 heavy chains and 4 light chains
2 heavy chains form a dimer driven by the
attraction of the hydrophobic amino acids of
these heavy chains.
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When ATP was added, the actin filaments began to glide along the surface.
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A myofibril is often as long as the
muscle cell itself.
Sarcomere
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Skeletal Muscle Myofibrils
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The Sliding-Filament Model of Muscle Contraction
The myosin heads are described as “walking” toward the
attached ends of the actin filaments.
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Accessory Proteins of Muscle Contraction
Titin: acts as a molecular spring to keep the myosin in the middle
of the sarcomere and allows the muscle fiber to recover after being
overstretched.
Nebulin: acts as a molecular ruler to determine the length of the
filament. It is an actin-binding protein.
Cap Z: anchors the plus end of the actin to the Z disc.
Tropomodulin: caps the minus end of the actin to prevent it from
depolymerizing.
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T tubules and the sarcoplasmic reticulum
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Increase in calcium ion concentration is fast (passed within milliseconds)
and momentary because the calcium ions are pumped back into the SR
thus allowing the myofibrils to relax.
Role of ATP: filament sliding and pumping of calcium ions
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Muscle Contraction Animation
Another Animation
25
A subtle mutation in cardiac myosin can cause familial hypertrophic
cardiomyopathy.
Different forms of cardiac muscle myosin and cardiac muscle actin are
expressed in the heart. . And changes that would not cause noticeable
consequences in other tissues cause serious heart problems.
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Familial hypertrophic cardiomyopathy is a frequent cause of sudden
death in young athletes.
Condition: heart enlargement, abnormally small coronary vessels and
cardiac arrhythmias.
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40 point mutations in genes encoding for cardiac myosin heavy chains
almost all causing changes in or near the motor domain of the myosin as
well as a dozen in other genes coding for contractile proteins such as the
myosin light chains, cardiac troponin and tropomyosin have been found
that cause the disease.
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