Muscle Physiology

Outline: Skeletal Muscle

1) Somatic Motor pathways

2) Neuromuscular junction (synapse)

3) Excitation of muscle cells

4) Contraction of muscle cells

5) Neural modulation of excitation-contraction

6) Variation in Skeletal muscle physiology

7) Energy sources for contraction

8) Effects of fatigue and exercise

Somatic Motor PathwaysPrimary Motor Cortex

Brainstem

Skeletal Muscle

Direct Pathways:

Fine Motor ControlMuscle Tone

Indirect Pathways:

PosturePositioningCoordination

Direct Pathways:

Fine Motor ControlMuscle Tone

Indirect Pathways:

PosturePositioningCoordination

Many muscles receive input from both pathways

Cerebellum: Coordination of Motor Output

Vestibulocerebellar

Posture & Balance

Spinocerebellar

Simple Movements

Cerebrocerebellar

Complex movements

Motor Commands Sensory feedback from proprioreceptors(muscle spindle and golgi organ)

Primary Motor Cortex

Neuromuscular Junction

Chemical synapse between Motor Neurons and Muscle Cells

Neuromuscular junction: Physiology

1) Action potential from Motor Neuron

2) VG Ca2+ channels open

3) Ca2+ influx

4) Vesicles of ACh release to synaptic cleft

5) ACh binds to ligand-gated Na+ channels on Muscle membrane

6) Na+ influx

7) Depolarization of Muscle cell EXCITABLE MEMBRANE

2

1

3

5

4

7

6

Depolarization of Muscle Cell

Resting

Depolarization

Repolarization

Resting

Dep

olar

izat

ion R

epolarizationEverything about muscle cell action potentials is identical to neurons (All-or-none, etc)!

Exception: RMP = -85 mV

So you have an excited muscle cell membrane……

Excitation of the muscle cell membrane leads to muscle

cell contraction via a mechanism called:

Excitation-Contraction Coupling

Muscle microanatomy

Bone

TendonMuscle

Muscle Fascicle Muscle Fiber

Myofibril

Myosin

Actin

Myofibrils contain the contractile mechanism of skeletal muscle

Functional organization of Myofibril:The Sacromere

MyosinActin

Sarcomere

Z-disk Z-diskCross-bridges

Sliding Filament Model: Contraction

Relaxed Muscle: large gap between actins

Resting Position of Z-disc

Contraction: gap between actins NARROWS

Maximal contraction: NO gap between actins

Sliding Filament Model: Generalizations

Actin & Myosin do not change length

Only Actin moves

Each Sacromere shortens VERY LITTLE

Relaxation is passive

How do sliding filaments result in whole muscle shortening and force?

Fascicle

Sacrolemna

Muscular Dystrophy = NO DYSTOPHIN!

Cross-Bridge Cycling : Mechanism of Sliding Filaments

MyosinActin

Sarcomere

Z-disk Z-disk

Cross-bridges

Actin: Activation

Tropomyosin TroponinActin

REST: active sites are not exposed

ACTIVATION: Ca2+ binds to Troponin Exposing active sites

Active Site

Where does Ca2+ come from?

Sarcoplasmic Reticulum

T-tubules

Sacrolemna

Muscle Fiber

Calcium initiates muscle contraction:Where does Ca2+ come from in Skeletal Muscle?

Sarcoplasmicreticulum

RyR

T-tubule

Ca2+ Stores

1

Myosin

Actin

DHP: VG-Ca2+

RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ channel

Sarcoplasmicreticulum

RyR

Ca2+ EFFLUX

Myosin

Actin

DHP: VG-Ca2+

RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ Receptors

Skeletal Muscle: Calcium Efflux from SR

Cross Bridge Cycling: What happens after Actin & Myosin Bind?

Muscle Cross Bridge Video

Cross-bridge Cycling: Striated & Smooth MuscleCross-bridge Cycling: Striated & Smooth Muscle

1 2 3 4 5

1) Cross-bridge Formation

Myosin head: loaded with potential energy

Myosin

Actin

Pi

ADP

Cross-bridge Cycling: Striated & Smooth Muscle

1 2 3 4 5

2) Power Stroke: Phosphate release

Stored Potential Energy is releasedMyosin

Pi

ADP

Actin SLIDES

Cross-bridge Cycling: Striated & Smooth Muscle

1 2 3 4 5

3) ADP dissociation

Myosin

Actin

ADP

Cross-bridge Cycling: Striated & Smooth Muscle

1 2 3 4 5

4) Rigor State

Myosin

Actin

Cross-bridge Cycling: Striated & Smooth Muscle

1 2 3 4 5

5) NEW ATP Binding: Myosin detaches

Myosin

Actin

ATP

Rigor Mortis

Myosin Cocking (between steps 5 & 1)1 2 3 4 5

ATP + H20 ADP + Pi + H+ + ENERGY

Hydrolysis by Myosin ATPase

Myosin Cocking

Once Cocked the Myosin head is loaded with POTENTIAL ENERGY

Muscle Contraction: Synthesis

1) Brain send AP down Motor pathways to Neuromuscular junction

2) Neuromuscular junction propagates AP to sarcolemna

3) AP on sacrolemna propagates down t-tubules into SR

4) SR releases Ca2+; Myosin & Actin bind

5) Cross-bridge cycling; Sliding Filaments

How muscles RELAX

Sarcoplasmic Reticulum

T-tubules

Sacrolemna

Muscle Fiber

1) Action Potential move along Sacrolemna

2) Action Potenial penetrates T-tubules & SR

3) VG Ca2+ in SR open, releasing Ca2+ onto Sarcomeres

4) Ca2+ binds to Troponin, exposing Actin’s active sites

5) Actin Binds to Myosin

1) Acetylcholine detaches from Na+ channels at Neuromuscular junction

2) Ca2+ is pumped (by Ca2+ ATPase pump!) back into Sacroplasmic Reticulum

Return to resting position : Titin

MyosinActin

Sarcomere

Z-disk Z-disk

Cross-bridges

http://www.fbs.leeds.ac.uk/research/contractility/titin.htm

TITIN

Muscle Contraction lead to FORCE

What do we know about MUSCLE FORCE?

Tension: how muscle develop force

Single MOTOR UNIT developing tension

Muscle twitch: contraction of motor unit in response to a single action potential

Stimulus applied Stimulus applied Stimulus applied

Muscle Twitches are All-or-None!

Motor Unit = a single motor neuron and all the muscle fibers it innervates

Muscle force can be altered 1) WITHIN SINGLE MOTOR UNITS 2) BETWEEN MULTIPLE MOTOR UNITS

Summation: Single Motor Unit

Stimulus applied Stimulus applied

Muscle fiber was not able to relax so tension increased

Summation occurs because Ca2+ is still bound to actin

2nd AP releases MORE Ca2+ causing more actin to be exposed to myosin heads

When action potentials come VERY RAPIDLY muscle fiber CANNOT relax

Unfused (Incomplete) Tetanus Fused (Complete) Tetanus

Summation & Tetanus allow Summation & Tetanus allow single motor unitssingle motor units to increase Tension (Force) to increase Tension (Force)

Motor Unit Recruitment

Different Motor Units can WORK TOGETHER to further increase force!

Tension varies with the starting length of the sacromere

Muscle Twitches

Variation in Muscle Fibers

TYPE 1

TYPE 2B

TYPE 2A

Fiber type is the same within a Motor Unit!!!!!!!!!!!!!!!!!!!!!!

WHITE MUSCLE

RED MUSCLE

WildType = normal rat TransGenic = rat with more Type I

TG rat has darker muscles due to more myoglobin, mitochondria

Myoglobin

Oxygen

Fiber types & Diameter underlie the trade-off between sprinting & marathon running in Humans

Maximum Running Distance

Max

imum

Run

ning

Spe

ed

100 m Dash olympian – Type 2B

Marathon olympian – Type 1

Energy Sources for Contraction1) ATP is needed to break cross-bridge2) ATP > ADP + P is needed to relax Myosin head3) P release from Myosin provides energy for Power stroke

Where does the ATP come from?Where does the ATP come from?

Aerobic RespirationAnaerobic RespirationCreatine

10 seconds10 seconds 3 minutes 3 minutes HoursHours