“How Do Muscles Contract?”. This theory states that during contraction, the thin filaments slide pass the thick filaments so that they over lap by a greater

“How Do Muscles Contract?”

This theory states that during contraction, the thin filaments slide pass the thick filaments so that they over lap by a greater degree.

The result is that the I bands shorten and the distance between the Z discs decrease.

The H band disappears and the A bands remain the same length.

Copyright © 2010 Pearson Education, Inc.

I

Fully relaxed sarcomere of a muscle fiber

Fully contracted sarcomere of a muscle fiber

IA

Z ZH

I IA

Z Z

1

2

For a muscle to contract, three events need to occur:a) The muscle needs to be stimulated by a nerve ending. This leads to a change in the membrane potential.The site of this is called the neuromuscular junction.

For a muscle to contract, three events need to occur: b) An electrical current (action potential) then needs to be generated along the sarcolemma.

For a muscle to contract, three events need to occur: c) The electrical current results in the final trigger which is a short lived rise in intracellular calcium ions which results in the in the contraction.


The nerve cells that activate skeletal muscle fibers at the neuromuscular junction called somatic (body) motor (think muscles) neurons.


The motor neurons reside in the spinal column and brain, they have long cyctoplasmic extensions called axons.


The motor neurons reside in the spinal column and brain, they have long cytoplasmic extensions called axons. These enter the muscle and divide extensively so that each muscle fiber (cell) has its own axon terminal which forms a neuromuscular junction.


Spinal cord

Motor neuroncell body

Muscle

Branching axonto motor unit

Nerve

Motorunit 1

Motorunit 2

Musclefibers

Motor neuronaxon

Axon terminals atneuromuscular junctions

Axons of motor neurons extend from the spinal cord to the muscle.There each axon divides into a number of axon terminals that formneuromuscular junctions with muscle fibers scattered throughoutthe muscle.

Branching axonterminals formneuromuscularjunctions, one permuscle fiber (photo-micrograph 330x).

(b)

(a)



The axon does NOT come into direct contact with the sacrolemma of the muscle fiber. T

There is a 1 to 2 nm cleft between them called the synaptic cleft. This cleft is not empty but is filled with a gel like extracellular matrix.



The nerve impulse is transmitted across this cleft by the release of a neurotransmitter. This crosses the space and attaches to specific membrane receptors on the sacrolemma.



The typical neurotransmitter found at these synaptic junctions is acetylcholine.


This molecule resides is vesicles in the axon and is released upon depolarization of the axon terminal.


These diffuse across the cleft and attach to receptors which then stimulate the depolarization of the muscle fiber.


Recall that all cells are polar, they are positively charged on the outside and negatively charged on the inside.

Sodium ions, Na+ are in high concentration on the outside and potassium ions, K+, are in high concentration on the inside.


Acetylcholine binds to its receptor on the sarcolemma and a gated ion channel is opened. This causes sodium ions to diffuse into the muscle fiber and potassium ions to diffuse out.


This is an autoimmune disease that specifically attacks the acetylcholine receptor.

Symptoms include: Weakness starting with the eye lids

(ptosis) Progressing to a general weakness Ends with difficulty swallowing and SOB


Curare competitively binds to the acetyl choline receptor but does not lead to depolarization.

Death from asphyxiation quickly follows



Action potential arrives at axon terminal of motor neuron.

Voltage-gated Ca2+

channels open and Ca2+ enters the axon terminal.

Ca2+ entry causes some synaptic vesicles to release their contents (acetylcholine)by exocytosis.

Acetylcholine, a neurotransmitter, diffuses across the synaptic cleft and binds to receptors in the sarcolemma.

Ca2+

Axon terminalof motor neuron

Synaptic vesiclecontaining ACh

Mitochondrion

Synaptic cleft

Junctionalfolds of

sarcolemma

Fusingsynaptic vesicles

ACh

Sarcoplasm of muscle fiber

Ca2+

1

2

3

4


Postsynaptic mem-brane ion channel opens; ions pass.

Na+ K+

5 ACh binding opens ion channels that allowsimultaneous passage of Na+ into the muscle fiber and K+ out of the muscle fiber.


The initial depolarization at the neuromuscular junction ignites an action potential that spreads out in all directions across the sarcolemma. The depolarization opens voltage- gated sodium channels.


As the polarization moves down the sarcolemma, other voltage gated channels are opened and the process continues.


Na+ K+

Axon terminal

Synapticcleft

ACh–

ACh

1 Local depolarization: generation of the end plate potential on the sarcolemma

Na+

Na+

Open Na+

Channel

Closed Na+Channel

Closed K+

Channel

Open K+Channel

K+

K+

K+

2 Generation and propagation ofthe action potential (AP)

3 RepolarizationSarcoplasm of muscle fiber

Na+


This process restores the resting potential.

The sodium channels initially opened by the depolarization close and at the same time a potassium channel opens, letting potassium to diffuse out of the cell, restoring the negative voltage inside the muscle fiber.


Na+ channelsclose, K+ channelsopen

K+ channelsclose

Repolarizationdue to K+ exit

Threshold

Na+

channelsopen

Depolarizationdue to Na+ entry


Before the muscle fiber contracts, there has to be an excitation coupling.

This is the sequence of steps where the action potential along the sarcolemma leads to changes in the levels of calcium ions which results in the mechanical contraction.

These are two sets of intracellular tubules that participate in the regulation of muscle contraction and excitation coupling.

These are found at each A and I band junction. A T-tubule (or transverse tubule), is a deep invagination of the plasma membrane (sarcolemma). These invaginations allow depolarization of the membrane quickly to the interior of the cell.

This is a modified smooth endoplasmic reticulum. Its tubules run longitudinally surround each myofibril. They communicate with each other in the H zone. They function to store calcium ions.


Axon terminalof motor neuron

Muscle fiberTriad

One sarcomere

Synaptic cleft

Setting the stage

Sarcolemma

Action potentialis generated

Terminal cisterna of SR ACh

Ca2+


Calciumions arereleased.

Steps inE-C Coupling:

Terminalcisterna of SR

Voltage-sensitivetubule protein

T tubule

Ca2+

releasechannel

Ca2+

Sarcolemma

Action potential ispropagated along thesarcolemma and downthe T tubules.

1

2

Myosin makes up the thick filament. This is a complex molecule that consists of two heavy and four light polypeptides.These form a molecule with a rod like tail with two flexible globular “heads”.


Flexible hinge region

Tail

Myosin head

ATP-bindingsite

Heads

Actin-binding sites

Thick filament

Each thick filament consists of many myosin moleculeswhose heads protrude at opposite ends of the filament.

Portion of a thick filament

Myosin molecule

Actin makes up the bulk of the thin filament. This molecule has ”kidney shaped” polypeptide subunits called globular actin or G actin which combine with the myosin head during the contracting process.

Troponin is a globular three polypeptide complex. It has several regulatory roles with actin.

TnI binds to actin TnT binds to Tropomyosin and helps to position

it on actin TnC binds calcium ions.

Tropomyosin a rod shaped protein which helps to stabilize the actin molecule. In a relaxed muscle fiber, they block myosin blinding sites on the actin molecule.


Tropomyosin Troponin Actin

Active sitesfor myosinattachmentActin subunits

Thin filament

A thin filament consists of two strands of actin subunitstwisted into a helix plus two types of regulatory proteins

(troponin and tropomyosin).

Portion of a thin filament

Actin subunits


Thinfilament

Thickfilament

In the center of the sarcomere, the thick filamentslack myosin heads. Myosin heads are present onlyin areas of myosin-actin overlap.

Longitudinal section of filaments within onesarcomere of a myofibril


Thin filament (actin) Thick filament (myosin)Myosin heads

Titin is the primary protein found in the elastic filament. This protein extends from the Z disc to the thick filament. It helps the muscle spring back to its original shape after stretching.


The cross bridge formation is the attachment of the myosin heads to the actin. This process requires calcium ions. Calcium is the key ion in the contraction process.


The muscle is relaxes when there are low levels of intracellular calcium ions. The myosin binding sites on the actin molecule are blocked by Tropomyosin proteins.


As intracellular calcium levels rise, the ions bind to regulatory sites on the protein troponin. This results in a change in troponin’s shape causing it to move the Tropomyosin off the myosin binding sites.


1. Myosin heads bind to the passive actin filaments at the myosin binding sites.


1. Myosin heads bind to the passive actin filaments at the myosin binding sites.

2. Upon strong binding, myosin and actin undergo an isomerization (myosin rotates at the myosin-actin interface) extending an extensible region in the neck of the myosin head.


Actin

Cross bridge formation.

Ca2+

1

Myosinhead

Thick filament

Thin filament

ADP

Myosin

Pi


The power (working) stroke.2

ADP

P i


3. Shortening occurs when the extensible region pulls the filaments across each other (like the shortening of a spring). Myosin remains attached to the actin.


3. Shortening occurs when the extensible region pulls the filaments across each other (like the shortening of a spring). Myosin remains attached to the actin.

4. The binding of ATP allows myosin to detach from actin. While detached, ATP hydrolysis occurs "recharging" the myosin head. If the actin binding sites are still available, myosin can bind actin again.


Cross bridge detachment.3

ATP


Cocking of myosin head.4

ATPhydrolysis

ADP

PI


Phase 1Muscle fiber isstimulated by motorneuron (see Figure 9.8).

Action potential (AP) arrives at axonterminal at neuromuscular junction

ACh released; binds to receptorson sarcolemma

Ion permeability of sarcolemma changes

Local change in membrane voltage(depolarization) occurs

Local depolarization (end platepotential) ignites AP in sarcolemma


AP travels across the entire sarcolemma

AP travels along T tubules

SR releases Ca2+; Ca2+ binds totroponin; myosin-binding sites(active sites) on actin exposed

Myosin heads bind to actin;contraction begins

Phase 2Excitation-contractioncoupling occurs (see Figures 9.9 and 9.11).


Illustrates the cross bridging requires ATP.



Most muscles stiffen 3 to 4 hours after death.




Calcium leaks into the cells, causing cross bridging.




Calcium leaks into the cells, causing cross bridging.

ATP is no longer being produced, leaving the muscles stiff.


Rigor mortis disappears after the muscle proteins begin to break down.

Documents

“How Do Muscles Contract?”. This theory states that during contraction, the thin filaments slide pass the thick filaments so that they over lap by a greater