Molecualr mechanism of Skeletal Muscle Contraction

A lecture on the moelcular mechanism of skeletal muscle contraction.

1. Molecular Mechanisms of
Contraction of Skeletal
Muscle
BME 45
Professor Lauren D. Black III

2. Outline of Today’s Class
•Characteristics of Whole Muscle Contraction
•Muscle Action Potential
•Excitation Contraction Coupling

3. Characteristics of Muscle Contraction
Skeletal Muscle Tone
•Even when muscles are at rest, a certain amount of
tautness usually remains. This is called muscle tone.
•Because normal skeletal muscle fibers do not contract
without an action potential to stimulate the fibers,
skeletal muscle tone results entirely from a low rate of
nerve impulses coming from the spinal cord.
•These, in turn, are controlled partly by signals
transmitted from the brain to the appropriate spinal
cord anterior motorneurons and partly by signals that
originate in muscle spindleslocated in the muscle
itself.

4. Characteristics of Muscle Contraction
"Coactivation" of Antagonist Muscles
•Virtually all body movements are caused by
simultaneous contraction of agonist and antagonist
muscles on opposite sides of joints.
•The position of each separate part of the body, such
as an arm or a leg, is determined by the relative
degrees of contraction of the agonist and antagonist
sets of muscles.
•Midpositionof limbs example.
•Thus, by varying the ratios of the degree of activation
of the agonist and antagonist muscles, the nervous
system directs the positioning of the arm or leg.

5. Characteristics of Muscle Contraction
Remodeling of Muscle to Match Function
•All the muscles of the body are continually being
remodeled to match the functions that are
required of them (diameters, lengths, strengths,
vascularization, fiber types –somewhat) and this
process can occur in the time span of only a few
weeks.
Muscle Hypertrophy
Muscle Atrophy
Adjustment of Muscle Length
Hyperplasia of Muscle Fibers
Muscle Denervation

6. Review/ Summary
•Skeletal muscle has a hierarchical structure.
•Calcium presence drives contraction.
•Sliding Filament theory described how actin and myosin interact to
generate physical contraction.
•Isotonic and Isometric measurements lead to different physical
relationships in muscles.
•Muscle force is controlled by a wide range of factors: calcium
concentration, number of fibers activated, the frequency of activation, etc.
•Muscle Tone is always present (for most of us).
•Muscles usually work in agonist pairs.
•Muscles are continuously remodeled.

7. Nerve Review and the NMJ
BME 45
Professor Lauren D. Black III

8. Nerve Review

9. Nerve Cell Structure

10. Action Potential

11. Ionic Basis of Action Potential

12. Action Potential
Voltage-Gated Sodium Channel-Activation and Inactivation and K+ of the Channel:

14. Excitation of Nerve AP
Excitation-The Process of Eliciting the
Action Potential
•Basically, any factor that causes sodium
ions to begin to diffuse inward through the
membrane in sufficient numbers can set
off automatic regenerative opening of the
sodium channels (mechanical, chemical,or
electrical).
•All these are used at different points in the
body to elicit nerve or muscle action
potentials:
•mechanical pressure to excite sensory nerve
endings in the skin,
•chemical neurotransmitters to transmit
signals from one neuron to the next in the
brain, and
•electrical current to transmit signals between
successive muscle cells in the heart and
intestine.

15. Synaptic
Transmission
Review

16. Electrical Synaptic Transmission
•Electrical Synapses are primarily gap junctions.
•Exist in cells throughout the body as low resistance pathways for
current to flow from one cell to another.
•Electrical synapses are bidirectional and act as a low-pass filter.
•Important for synchronization of activity in neural networks –
particularly in CNS.

17. Chemical Synaptic Transmission
Chemical Receptor Type Receptor Location
Key Agonists,
Antagonists, and
Potentiators
**
Acetylcholine (ACh)Cholinergic
Nicotinic (nAChR)ICR‡(Na+,K+)(Na+,K+)
Skeletal muscles,
autonomic neurons, CNS
Agonist:nicotine
Antagonists:curare,α-
bungarotoxin
Muscarinic (M) GPCR
Smooth and cardiac
muscle, endocrine and
exocrine glands, CNS
Agonist:muscarine
Antagonist:atropine
Amines
Norepinephrine (NE)
Epinephrine (E)
Adrenergic(α,β)(α,β)GPCR
Smooth and cardiac
muscle, glands, CNS
Antagonists:
α-
receptors: ergotamine,
phentolamine.
β-receptors:propranolol
Dopamine (DA) Dopamine (D) GPCR CNS
Agonist:bromocriptine
Antagonists:antipsychot
ic drugs
Serotonin (5-
hydroxytryptamine, 5-
HT)
Serotonergic (5-HT)
ICR(Na+,K+),(Na+,K+),G
PCR
CNS
Agonist:sumatriptan
Antagonist:LSD
Histamine Histamine (H) GPCR CNS
Antagonists:ranitidine
(Zantac®) and cimetidine
(Tagamet®)

18. Chemical Synaptic Transmission
Amino Acids
Glutamate
Glutaminergic ionotropic
(iGluR)
AMPA ICR(Na+,K+)(Na+,K+)CNS Agonist:quisqualate
NMDA ICR(Na+,K+)(Na+,K+)CNS Potentiator:serine
Glutaminergic
metabotropic (mGluR)
GPCR CNS Potentiator:glycine
GABA(γ-aminobutyric
acid)(γ-aminobutyric
acid)
GABA ICR(Cl−),(Cl−),GPCR CNS
Antagonist:picrotoxin
Potentiators:alcohol,
barbiturates
Glycine Glycine (GlyR) ICR(Cl−)(Cl−) CNS Antagonist:strychnine
Purines
Adenosine Purine (P) GPCR CNS
Gases
Nitric oxide (NO)None N/A N/A
*This table does not include the numerous peptides that can act as neurocrines.
**This list does not include many chemicals that are used as agonists and antagonists in physiological research.
‡ICR=ion channel-receptor;ICR=ion channel -receptor;GPCR=G protein-coupled receptor;GPCR=G protein -coupled
receptor;AMPA=α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid;AMPA=α-amino-3-hydroxy-5-methylisoxazole-4-
proprionic acid;NMDA=NMDA=n-methyl-d-aspartate;LSD=lysergic acid diethylamide;LSD=lysergic acid diethylamide;N/a=not
applicable.

19. Neuropeptide Transmitters

20. Neurotransmitter Receptors

21. Chemical Synaptic Transmission

22. The NMJ
•Recall that a motor pathway is a single motorneuronthat synapses with
the muscle

23. The NMJ

24. Neuromuscular Junction

25. Muscle Action Potential
•Almost everything we previously discussed regarding
initiation and conduction of action potentials in nerve fibers
applies equally to skeletal muscle fibers, except for
quantitative differences.
•Some of the quantitative aspects of muscle potentials are
the following:
•Resting membrane potential: about -80 to -90 millivoltsin skeletal
fibers-the same as in large myelinatednerve fibers.
•Duration of action potential: 1 to 5 milliseconds in skeletal muscle-
about five times as long as in large myelinated nerves.
•Velocity of conduction: 3 to 5 m/sec-about 1/13 the velocity of
conduction in the large myelinated nerve fibers that excite skeletal
muscle.

26. Muscle Action Potential
.

27. Excitation Contraction Coupling

28. Excitation Contraction Coupling
•Once the calcium ions have been released from
the sarcoplasmic tubules and have diffused
among the myofibrils, muscle contraction
continues as long asthe calcium ions remain in
high concentration.
•However, a continually active calcium pump
located in the walls of the sarcoplasmic
reticulum pumps calcium ions away from the
myofibrils back into the sarcoplasmictubules.
•This pump can concentrate the calcium ions
about 10,000-fold inside the tubules. In addition,
inside the reticulum is a protein called
calsequestrinthat can bind up to 40 times more
calcium.

29. Nerve/ NMJ Review/ Summary
•Action Potentials, their shape and the ionic basis
•Synaptic Transmission
•Muscle Action Potential Differences.
•Excitation-contractioncoupling