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Myosin Contracts Skeletal Muscle . Jonathan P. Davis, Ph.D. Assistant Professor Office/Lab Phone 247-2559 Email: [email protected]. Department of Physiology and Cell Biology, The Ohio State University, 400 Hamilton Hall. Muscle. - PowerPoint PPT Presentation
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Myosin Contracts Skeletal Muscle
Jonathan P. Davis, Ph.D. Assistant Professor
Office/Lab Phone 247-2559
Email: [email protected]
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+]Plasma M
embran
e
Plasma Membrane
T-Tubule
Sarco
plasm
ic Reti
culum
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
CD
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 muscleb. Lever system