• Topics– Role of calcium– Muscle fiber membrane potential & contraction– Neural control of muscle & reflexes– Whole muscle physiology

Role of calcium

Troponin complex

Tropomyosin

•Troponin and Tropomyosin bind to actinblock the actin – myosin binding sites

•Troponin is a calcium binding protein

• When Troponin binds calcium it moves Tropomyosin away from the actin-myosin binding site

CaCa

Where does Calcium come from?

• Intracellular storage called Sarcoplasmic Reticulum

• Surround each myofibril of the whole muscle• Contains high concentration of calcium

• Transverse Tubules connects plasma membrane to deep inside muscle

Myofibril

Sarcoplasmic Reticulum

Transverse tubules

Transverse tubules

• So far:– Actin and myosin will bind to each other– Troponin / tropomyosin inhibit this– Calcium removes inhibition

What controls muscle calcium?

• What else do we know?– Neurons initiate muscle contraction at NMJs

by generating postsynaptic potentials

(some muscle fibers have APs)

• Maybe muscle membrane potential is important

Muscle fiber

Tension

VmStimulate nerve

Te

nsio

n

Vm

Time

Muscle AP

Force Transducer

Excitation-Contraction coupling:1

‘twitch’

Vm

Tension

Force TransducerVary [K+] outside

Vm (mV)

Ten

sion

1.0

0-70 -60 -50 -40 -30

Conclusion: Muscle contraction occurs with Vm depolarization

Muscle fiber

Excitation-Contraction coupling:2

Why T-tubules important?Stimulate near T-tubule see contractionof adjoining sarcomeres

No contractions

T-tubule ‘Local stimulation’

Motor nerve

Neurotransmitter receptors

Membrane depolarization or APs carried deep into the muscle by T-tubules

+

T-tubule

SR

Text Fig 10-21Myofibril

Sarcoplasmic Reticulum

Transverse tubules

Transverse tubules

MyT-tubule

SR

SR

Ryanodine Receptor

Dihydropyridine receptor

myoplasm

T-tubule(extracellular)

SR

Myoplasm(intracellular)

++

++++

Ca++Ca++Ca++

_ _ _

+++

_ _ _+++

Ca++ pump

1. Synaptic Depolarization of the plasma membrane is carried into the muscle by T-Tubules

2. Conformational change of dihydropyridine receptor directly opens the ryanodine receptor calcium channel

3. Calcium flows into myoplasm where it binds troponin

4. Calcium pumped back into SR

Summary of events

• Neural Control of Muscle– Voluntary– Reflex

Neural control of muscle contraction

Motor Pool: all of the motor neurons that innervate a single muscle

Motor Unit: single motor neuron and all the muscle fibers it innervates– a few fibers 1000s of fibers

• Size of the motor units determines precision of movementFingers have small motor units, legs have big

motor units

• Recruitment of twitch fibers• Smallest motor units to a single muscle are

recruited first• Why?

Allow smooth generation of movement

First

Little force

Second

More force Even more force

Third

1+2+3 = maximum force

Whole muscle

Individual myofibrils

Motor neurons

Reflex control of muscle contraction

Two sensory receptors

1. Muscle Spindle• Monitors muscle length

2. Golgi Tendon Organ• Monitors muscle tension

Muscle Spindle

Motorneurons

Group I and IISensory fibers

IntrafusalMuscle fibers

ExtrafusalMuscle fibers

Muscle Spindle

Motor neurons

Muscle spindle

Extrafusal muscle fibers

nerve

motor neurons innervate extrafusal muscle fibers and cause the muscle to contract

motor neurons innervate only the intrafusal muscle fibers and cause them to contract

• The sensory endings in the muscle spindle are activated by muscle lengthening

Isolated muscleIa sensoryneuron

Motor neurons

Muscle stretch

Muscle length

APs insensory

APs inmotor

Spinal cord

Longer

AP

AP

Effect of muscle spindle

• When muscle stretches, spindle stretches1. Increase APs in 1a sensory neuron

2. Increase APs in motor neuron

3. Muscle contracts and returns to original length (almost)

• When muscle contracts, spindle shortens– Might expect activity of spindle to decrease

• BUT– To maintain sensitivity of the spindle, the

intrafusal fibers also contract– Controlled by motor neurons

Muscle Spindle

Motor neurons

ExtrafusalMuscle fibers

Motorneurons

Group I and IISensory fibers

IntrafusalMuscle fibers

Muscle length

longer

shorter

Motor neuron

Ia sensoryneuronstimulate

record

APs in sensory - Motor neuron only

Muscle length

longer

shorter

Motor neuron

Ia sensoryneuronstimulate

record

Motor neuron

APs in sensory - Motor neuron only

APs in sensory - and Motor neurons

Muscle Spindle motor neurons

• permit muscle spindle to function at all muscle lengths

• Maintains sensitivity of the spindle

Ia sensoryneuron

Muscle spindle

Motor neurons

Inhibitory interneuron

Spinal cord

Golgi Tendon Organ

• Operates like muscle spindle, but monitors muscle tension (force)

• Negative feedback because they inhibit the muscle they are located in

APs from GTO

Muscle length

longer

shorter

Increased APs during contraction

Very little at rest

Golgi Tendon Organ

Ib sensoryneuron

Golgi tendon organ

Motor neurons

Inhibitory

interneuron

Spinal cord

Muscle Spindle Response Tendon Organ Response

Passive Stretch Increase APs Decrease APs

Active Contraction No change Increase APs

Summary

• Muscle Spindles– Monitor muscle length– When activated cause contraction

• Golgi Tendon Organ– Monitor muscle tension– When activated reduce contraction

Whole muscle physiology

• Types of skeletal muscle fibers

• Neural control of muscle contraction

• Production of force

Classification of muscle fiber types

1. Electrical properties of muscle membrane – do muscles have APs?

2. Maximal rate of contraction (Vmax) • determined by myosin ATPase activity

3. Density of SR calcium pumps

4. Density of mitochondria and blood supply

Vertebrate Skeletal Muscle Fiber Types:

1. Tonic

2. Twitch (or Phasic)a. Slow oxidative (Type I)

b. Fast oxidative (Type IIa)

c. Fast glycolytic (Type IIb)

• Tonic fibers– Very slow contractions– Do not produce APs do not twitch– Postural muscles

Twitch muscles• Slow oxidative (Type I)

– Contract slowly– Resist fatigue – Postural

• Fast Oxidative– High rate of contraction– Moderately resistant to fatigue– Rapid, repetitive motion (flight muscles migratory

birds)

• Fast Glycolytic– Rapid contraction– Rapid fatigue

Non-twitch fibers

• Many arthropods (crayfish, insects) do not have muscle APs

• Rather they have graded synaptic potentials

• Calcium released from SR in graded manner

• Degree of contraction depends on summation and facilitation of neural input

Te

nsio

n

Vm

Time

Muscle AP

Te

nsio

n

Vm

Time

Summation of Synaptic Potential

Non-twitch fibers

• Graded potential graded contraction

• Even large motor units can have precise contraction

Twitches and Tetanus

• The amount of force generated varies with frequency of neural APs

• Under low frequency neural AP, muscle will contract and relax – Single twitches

• If neural APs arrive before muscle can relax, the forces generated are additive

• At highest frequencies the muscle does not relax– tetanus

Twitches and Tetanus

Temporal Summation (20Hz)

Single twitches (5 Hz)

Unfused Tetanus (80Hz)

Fused Tetanus (100 Hz)

Ten

sion

Time

Te

nsio

n

Vm

‘twitch’Muscle AP

Timelatency

• Why latency?– In part due to time for all biochemical

reactions– Also due to elastic components of the muscle

• Tendons, connective tissue, cross-bridge links

Contractile component

Series elasticcomponent

Parallel ElasticComponent

Rest Contraction initiated

•Sarcomere shortens•Series elastic component stretches •but no muscle shortening

Tension generation

•Sarcomere shortens further

•muscle shortens

Text fig 10-26

Whole muscle summary

• 4 types of skeletal muscle fibers

• Neural control of contraction– Twitches and tetanus– Motor units & size principal

• Generation of muscle force– Elastic components of muscle

• Non-twitch muscles– Graded contractions

Muscle Diseases

• Duchenne muscular dystrophy– Muscle wasting disease– Affects 1 in 3500 boys– Life expectancy ~20 years

• Genetic disease– Complete absence of the protein ‘dystrophin’

Muscle plasma membrane

Dystrophin

Actin cytoskeleton(not actin thin filaments)

Dystroglycan Dystroglycan

Grb2Acetylcholine receptor

Potential protein associations of dystrophinExtracellular matrix

• There are many effects of dystrophin absence including:– Altered calcium handling (too much)– Membrane destabilization (too permeable)– Susceptibility to mechanical damage

• Effects on neuromuscular physiology– Altered nACH receptor clusters– Reduced mepp size

Force is proportional to cross-sectional area