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 actin block 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 Ca

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

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 Vm Stimulate nerve Tension Vm Time Muscle AP Force Transducer Excitation-Contraction coupling:1 ‘twitch’

Vm Tension Force Transducer Vary [K+] outside Vm (mV) Tension Conclusion: Muscle contraction occurs with Vm depolarization Muscle fiber Excitation-Contraction coupling:2

Why T-tubules important? Stimulate near T-tubule see contraction of 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 Myofibril Sarcoplasmic Reticulum Transverse tubules

My T-tubule SR Ryanodine Receptor Dihydropyridine receptor myoplasm

T-tubule (extracellular) SR Myoplasm (intracellular) 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 movement  Fingers 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 = 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  Motor neurons Group I and II Sensory fibers Intrafusal Muscle fibers Extrafusal Muscle 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 muscle Ia sensory neuron  Motor neurons Muscle stretch Muscle length APs in sensory APs in motor Spinal cord Longer  AP

Effect of muscle spindle When muscle stretches, spindle stretches 1.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 Extrafusal Muscle fibers  Motor neurons Group I and II Sensory fibers Intrafusal Muscle fibers

Muscle length longer shorter  Motor neuron Ia sensory neuron stimulate record APs in sensory -  Motor neuron only

Muscle length longer shorter  Motor neuron Ia sensory neuron stimulate 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 sensory neuron 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 sensory neuron Golgi tendon organ  Motor neurons Inhibitory interneuron Spinal cord

MuscleSpindle 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

Tension Vm Time Muscle AP Tension 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) Tension Time

Tension Vm ‘twitch’ Muscle AP Time latency 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 elastic component Parallel Elastic Component

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 Grb2 Acetylcholine receptor Potential protein associations of dystrophin Extracellular 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