1. Kinetics of Muscle Contraction and Relaxation
Bin Liu
Ph.D.
Phone: (614)
DHLRI 525
Department of Physiology and Cell Biology, The Ohio State University

2. Factors Controlling SPEED of Movement
Environmental
Whole Body
Muscle (Organ)
Muscle (Cellular)
Muscle (Molecular)

3. Ultimate Factors Controlling SPEED

4. Need the Strength to Meet the Demand Motor Units and Recruitment

5. Amplifying Velocity/Distance - Lever Systems, Muscle Length and Geometry
Levers Detrimental to Force
Levers Amplify Distance/Velocity

6. Energy Supply Also Controls SPEED
Glycolytic Sources SUPPORT Speed BUT NOT Duration
Oxidation Sustains Duration BUT NOT Speed

7. Striding Requires Contraction and Relaxation
For Sustained SPEEDS the Muscle Groups Must Contract as well as Relax – Otherwise No Continued Movement

8. SPEED Is Determined by Fiber Types and Fatigue
Different Fiber Types Contract and Relax at Different Rates
Fatigue Can Slow the Rates of Contraction and Relaxation – Again a Fiber Type Phenomenon

9. Cellular Regulation of Muscle Contraction
1) Action Potential
2) Calcium Transient
Plasma Membrane
Plasma Membrane
Sarcoplasmic Reticulum
[Ca2+]
T-Tubule
Sarcoplasmic Reticulum
SR Ca2+ ATPase
Time
Calcium
3) Calcium Binds Troponin C
4) Myosin Power Stroke
5) Force Production
Actin
Actin
–Ca2+ Relaxed
Tropomyosin
Troponin Complex
- Ca2+
Actin
Myosin
Myosin
+ Ca2+
Myosin Binding Site
+Ca2+ Contracted
ATP Driven
Power Stroke

10. The Action Potential, Rise in Calcium and Activation of the Thin Filament All Occur Much Faster than Contraction
Calcium Transient
(Shortening or Force Generation)

11. Biochemical Rate Limiting Step of Contraction
(Coupling of the Chemical Changes to Mechanical Changes)
Rate-Limiting Step for Contraction
The Myosin Neck is also a Lever Arm
POWER STROKE Associated with Pi Release

12. ATPase Rate Correlates with Maximal Speed of Muscle Contraction

13. The Load that Myosin Has to Work Against Alters Velocity
Maximal Velocity (VMAX)
Tug-of-War
To bear the load more myosins need to be simultaneously bound leading to drag. D A C B B A C
Even at the single molecule level velocity slows due to ADP release slowing with load. D

14. Different Fiber Types Contract and RELAX at Different Rates
- ADP
~250 Hz
Super Fast
Fast
Slow
~200 Hz
~90 Hz
~5 Hz
~2 Hz

15. 1 3 2 Ca2+ Off TnC Cross Bridge Dissociation
Three Biochemical Influences on Striated Muscle Relaxation 1 2 3
Fall in the Ca2+ Transient
Ca2+ Off TnC
Cross Bridge Dissociation
Actin
Actin
Tropomyosin
Troponin Complex
[Ca2+]
- Ca2+
Amp
Actin
Myosin
Myosin
Time
Time
+ Ca2+
Myosin Binding Site
ATP Driven
Power Stroke

16. Inhibition of the SR Ca2+-ATPase Inhibits Relaxation: Ca2+ Levels Must Decline for Relaxation to Occur
TBQ Inhibition of SR Ca2+-ATPase X X
SR Ca2+ ATPase
Control

17. Parvalbumin Acts as a Delayed and Temporary Ca2+ Buffer
Parvalbumin Increases the Rate of Muscle Relaxation by Giving the SR Ca2+-ATPase a Helping EF-Hand
+Parv
- Parv
Parvalbumin Acts as a Delayed and Temporary Ca2+ Buffer
Mg-Parv
Ca-Parv
Ca2+ Displaces Mg2+ from Parv
SR Ca2+ ATPase
SR Removes Ca2+ from Parv

18. The EF-Hand is the Most Common Calcium Binding Motif used to Decode the Calcium Signal
Crystal Structure of Cardiac TnC
EF-Hand
Canonical Calcium Binding Loop
N-Terminal Regulatory Domain
Loop
Helix
Helix
C-Terminal Structural Domain
> 500 known EF-hand proteins with >300 unique sequences
What is the significance? >1000-fold variation in affinity and rate constants

19. The Regulatory Domain of Troponin C Acts as a Ca2+ Dependent Switch
The Troponin Complex Contains Three Proteins
Ca2+
Troponin C – Binds Calcium
Troponin I – Inhibits Cross-Bridge Binding
Troponin T – Binds Tropomyosin
Ca2+
TnI
Apo State
Ca2+ Saturated
Ca2+ Saturated + TnI

20. Effect of ‘Slower’ or ‘Faster’ Troponin C Mutants on Skeletal Muscle Relaxation
Ca2+ Dissociation Rates from Fluorescent TnC Mutants
Rates of Relaxation with TnC Mutants
Control TnC
Slower TnC (5/s)
Faster TnC
Slower TnC
control TnC (11/s)
Faster TnC (16/s)

21. CLASSIFICATION OF SKELETAL MUSCLE FIBERS - All Systems “TUNED” for a Particular Function -
Classification system of muscle fibers is based on:
Rate of ATP utilization and capacity to re-synthesize ATP
Physiological implications of these parameters
Muscles are heterogeneous with different proportions of fiber types depending on function

22. Assorted References (contact me if you would like more)
Studies in Biology #11: Muscle. 2nd Edition, D.R. Wilkie 1979.
Human Physiology, 9th edition by E.P. Widmaier, H. Raff and K.T. Strang, 2004
News Physiol Sci Apr;16: Skeletal and cardiac muscle contractile activation: tropomyosin "rocks and rolls". Gordon AM, Regnier M, Homsher E.
Pflugers Arch Mar;449(6): Epub 2004 Nov 30. Sarcomeric determinants of striated muscle relaxation kinetics.
Poggesi C, Tesi C, Stehle R.
Annu Rev Physiol. 2005;67: Calcium, thin filaments, and the integrative biology of cardiac contractility.
Kobayashi T, Solaro RJ.
Am J Physiol Feb;270(2 Pt 1):C Parvalbumin relaxes frog skeletal muscle when sarcoplasmic reticulum
Ca(2+)-ATPase is inhibited. Jiang Y, Johnson JD, Rall JA.
Annu Rev Physiol. 2006;68: ; Design and Function of Superfast Muscles: New Insights into the
Physiology of Skeletal Muscle. Rome LC.