Myosin Contracts Skeletal Muscle

Jonathan P. Davis, Ph.D. Assistant Professor

Office/Lab Phone 247-2559

Email: davis.812@osu.edu

Department of Physiology and Cell Biology, The Ohio State University, 400 Hamilton Hall

MuscleSkeletal Cardiac Smooth

Thick Filament or Myosin Regulation

In these cases: Myosin needs to be “activated” before it can interact with actin or move cargo

Actin Binding Proteins Like Tropomyosin Regulate Myosin Thin Filament Regulation

Weak Electrostatic Myosin Binding Sites

Strong Hydrophobic Myosin Binding Sites

“Blocked State” “Closed State” “Open or M State”

Tropomyosin “Rocks and Rolls”

Structure of Skeletal (striated) Muscle Comprised of fibers (cells) Each fiber contains many myofibrils in parallel Each myofibril contains many sarcomeres in

series Striations due to characteristic banding pattern

of sarcomere

Electron micrograph of Skeletal Muscle Fiber

Sarcomere Composed of Overlapping Thin and Thick Filaments

The Sarcomere

CROSS-BRIDGES PROJECT FROM THICK TO THIN FILAMENTS

Z Line

Cross-bridge

H-Zone

The Thin Filament Is Composed Primarily of Actin but Also Contains Tropomyosin and the Troponin Complex

1) Troponin C – Binds Calcium2) Troponin I – Inhibits Cross-Bridge Binding3) Troponin T – Binds Tropomyosin

Complex

The Troponin Complex Contains Three Proteins

The transverse tubules bringaction potentials into the interior of the skeletal muscle fibers, so that the wave of depolarization passes closeto the sarcoplasmic reticulum,stimulating the release of calcium ions.

The extensive meshworkof sarcoplasmic reticulum assures that when it releases calcium ions they can readily diffuseto all of the troponin sites.

T-tubules and the Sarcoplasmic Reticulum

Cell Membrane

T -Tubule

Sarcoplasmic Reticulum

ACTION POTENTIAL CAUSES RELEASE OF CALCIUM FROM SR

Calcium

SR Ca2+ ATPase

Ryanodine Receptor

Dihydropyridine ReceptorCalsequestrin

Mechanism of Skeletal Muscle Activation by Ca2+

1) “off” state- absence of Ca2+

Tm blocks myosin binding

2) “on” state- Ca2+ binds to TnC Tm moves toward center of actin Myosin binding sites exposed Muscle contracts

**Tm can occupy 2 positions: “off” and “on” state

Time

[Ca2+]Plasm

a M

embra

ne

Plasma Membrane

T-Tubule

Sarco

plas

mic

Ret

icul

um Sarcoplasmic Reticulum

Regulation of Striated Muscle Contraction

1) Action Potential 2) Calcium Transient

Calcium

3) Calcium Binds Troponin C

Actin

TropomyosinTroponin Complex

- Ca2+

+ Ca2+ Myosin Binding Site

4) Myosin Power Stroke

*** ATP Driven Power Stroke & Detachment***

Actin

Myosin

Actin

Myosin

5) Force Production

–Ca2+ Relaxed

+Ca2+ Contracted

**SR Ca2+ ATPase**

Greater the force against which shortening occurs, the slower the velocity of shortening

Muscles exhibit > 200-fold variation in maximum velocity of shortening. Why?Maximum velocity of shortening

Reflects speed of cross-bridge cyclingIs actomyosin ATPase activityIs determined by differences in the myosin molecule

ISOTONIC AND ISOMETRIC CONTRACTIONS

A – 100% Maximal Force

B – 75% Maximal Force

C – 50% Maximal Force

D – 25% Maximal Force

A

B

C

D

A

B

C

D

Maximal Velocity (VMAX)Force

Muscle Shortening

Time

= L/T

RELATIONSHIP OF ELECTRICAL TO MECHANICAL EVENT IN SKELETAL MUSCLE CONTRACTION

Calcium Transient

(Shortening or Force Generation)

FORCE DEVELOPMENT IN AN ISOMETRIC CONTRACTION AS A FUNCTION OF STIMULUS FREQUENCY

Isometric contraction at each length

In the bodySkeletal muscle operates at plateau of length-force relationCardiac muscle operates on the ascending limb of length-force relation

ACTIVE, PASSIVE AND TOTAL FORCE VERSUS MUSCLE LENGTH

MECHANISM OF LENGTH-FORCE RELATIONSHIP IN MUSCLE

CLASSIFICATION OF SKELETAL MUSCLE FIBERS

Classification system of muscle fibers is based on:Rate of ATP utilization and capacity to re-synthesize ATPPhysiological implications of these parameters

Muscles are heterogeneous with different proportions of fiber types depending on function

RELATIONSHIP OF MOTOR UNITS TO INNERVATED MUSCLE FIBERS AND RECRUITMENT

Slow-oxidative

Fast-oxidative

Fast-glycolytic

LEVER RELATIONSHIP OF MUSCLE TO BONE AFFECTS FORCE DEVELOPMENT AND VELOCITY

EFFECTS OF FATIGUE ON SKELETAL MUSCLE FIBERS TYPES

What Could be Happening?1) Conduction Failure2) Energy Metabolism Biproducts A) Lactic Acid B) Phosphate and ADP

III. Geometry of Musclea. Direction fibers run in the muscle

b. Lever system