Lecture 13: Muscle II

I. Contraction of Skeletal Muscle

Sliding Theory of Contraction: during contraction, thin filaments slide past thick ones so that actin and myosin filaments overlap to a greater degree

A. Overview

1. Prior to contraction

            a. Cross bridges are disengaged

            b. All bands distinct

2. Nerve impulse initiates contraction

3. Cross bridges engage

4. ATP splits

            a. Energy used for swinging of cross bridges

5. Actin filaments pulled together

            a. H zone and Z disc smaller or lost

6. I band reduced

7. Cross bridges disengage

8. Crossbridges and actin filaments return to original position


II. Specifics of Contraction

A. During relaxed state

1. Ca2+ concentration in sarcoplasm is low

a. Ca2+ is stored in sacroplasmic tubules

2. Troponin-tropomyosin complex attached to actin filament

            a. Tropomyosin positioned to block myosin binding sites on actin filament

3. ATP and inactive ATPase bound to myosin head

            a. Low energy configuration

                        i. Binding to actin is not possible

B. Events during contraction

1. Nerve impulse (afferent signal) from motor neuron generates action potential in nerve cell

            a. AP propagated along sarcolemma and down T tubules

2. Myosin ATPase activated

            a. ATP splits

                        i. High energy myosin-ADP complex

3. AP causes release of Ca2+ from sarcoplasmic reticulum

4. Ca2+ binds to troponin

            a. Molecular shape of troponin changes

i. Tropomyosin is removed from binding site of mysosin on the actin filament

            b. Myosin attaches to actin

5. Contraction: Potential energy stored in high-energy configuration is used to pivot myosin head

            a. Myosin head bends as it pulls on actin

            b. ADP and inorganic phosphate are released from myosin

6. New ATP attached to myosin head

            a. Cross bridge simultaneously detaches

            b. Following death, no ATP and muscle fibers cannot relax

                        i. Rigor mortis

7. If no new impulse, Ca2+ is pumped back into sarcoplasmic reticulum (SR)

            a. Relaxation occurs

8. If Ca2+ present from additional impulse, cycle repeats

            a. Myosin head “steps” to next binding site on actin


III. Regulation of Contraction


A. Neuromuscular junction—functional connection between somatic nervous system and muscles

1. Motor neuron axons bifurcate to form multiple endings

            a. Separate endings synapse with individual nerve fibers

                        i. Each nerve fiber synapses with only a single motor neuron

                        ii. Motor neurons can synapse with multiple nerve fibers

2. Synapse—site of communication between neuron and muscle (neuron to neuron in nervous system)

            a. Contact is not direct

                        i. Physical separation—synaptic cleft

            b. Requires signal to be transduced into a chemical signal

                        i. Neurotransmitter

                        ii. ACh is NT at neuromuscular junction

3. Motor end plate—physical modification of sarcolemma where neuron synapses with fiber

            a. ACh receptors located on motor end plate

B. Transduction events:

1. Nerve impulse from somatic NS

2. ACh released from pre-synaptic motor neuron

3. ACh binds to receptors

            a. Na+ channels open

b. Inward depolarizing current initiates an action potential (see subsequent lectures on neurophysiology)

c. ACh is enzymatically destroyed

            i. Acetylcholinesterase

4. Action potential is propagated along sarcolemma and down T tubules

5. Ca2+ is released from SR (see above for resulting effects)

6. Ca2+ is removed by continuously active Ca2+ pumps

            a. At low enough concentrations, contraction ceases

7. At the level of individual muscle fibers (cells), contraction is all or nothing

a. In response to threshold stimuli, action potentials are generated in a non-graded fashion

8. Refractory period—cells must re-polarize before another AP can occur


IV. Contraction of Skeletal Muscle

A. Motor Unit—functional unit; a single motor neuron and all the muscle fibers it supplies

1. Distribution of fibers in a single motor unit is spread throughout a muscle

            a. Stimulation of a single motor neuron weakly contracts entire muscle

B. Muscle twitch—response of a muscle to a single supra-threshold stimulus

1. Phases (3)

            a. Latent phase (a few msec)

                        i. Onset of stimulus

                        ii. No measured contractile activity

                        iii. Excitation-contraction coupling

            b. Contraction phase (10-100 msec)

                        i. Onset of shortening to peak contraction

                        ii. If pull greater than load, muscle shortens

            c. Relaxation phase (10-100 msec)

                        i. Re-entry of Ca2+ into SR

                        ii. Muscle tension gradually returns to zero

2. Temporal characteristics vary among muscles

C. Graded muscle responses—variation in degree of contraction

1. Gradation results from:

            a. Altering stimulation frequency


            b. Altering stimulus strength


2. Response to frequency of stimulation

            a. Temporal (wave) summation

                        i. Strength of contraction increases with successive stimuli

ii. Muscles that are already contracted, contract further with additional Ca2+

iii. If stimulation is delivered prior to relaxation, contraction s are summed

b. Tetanus: At sufficiently high frequencies, no muscle relaxation occurs and contractions fuse into a smooth, sustained contraction

3. Motor unit summation—response to increasing stimulus intensity

            a. Primary mechanism for increasing force of contraction

            b. Multiple motor unit summation—Recruitment

            c. At threshold stimulation, first muscle contraction occurs

            d. As stimulus intensity is increased, additional motor units are activated

            e. Maximal stimulus

                        i. Strongest stimulus that causes increased contraction

            f. Accomplished by increased neural activation

4. Treppe—force of contraction increases during response to stimuli at the same strength

            a. Result of increasing Ca2+ availability

            b. Heat created during contraction increases efficiency of muscle enzymes

                        i. Warming up prior to athletic activity

5. Isotonic and Isometric contractions

            a. Terms:

                        i. Muscle tension—force of contracting muscle on an object

                        ii. Load—reciprocal force exerted by the object

            b. To move a load, muscle tension must be greater than load

            c. Isotonic contractions—muscle changes in length and moves load

                        i. Concentric—muscle shortens and does work

                        ii. Eccentric—muscle contracts as it lengthens

                        iii. Concentric and eccentric contractions occur can occur at the same time

iv. Eccentric contractions put the muscle in position to contract concentrically

            d. Isometric contractions—tension increases but the muscle length stays constant

                        i. Load greater than force

                        ii. Maintenance of posture

iii. Most real-life movements involve both isometric and isotonic contraction


V. Muscle Metabolism

A. ATP is the sole source of energy for contraction

B. Little ATP is stored but it is regenerated (recycled) rapidly

1. Direct phosphorylation of ADP by creatine phosphate

2. Anaerobic glycolysis

a. In the absence of oxygen, glycolytic products (pyruvic acid) are metabolized to lactic acid producing additional small quantities of ATP

3. Aerobic respiration

            a. 95% of ATP during light exercise

b. In presence of oxygen, products of glycolysis are broken down entirely with the generation of significant amounts of ATP

4. Glycogen is the source of glucose for both aerobic and anaerobic metabolism


VI. Force, Velocity and Duration of Muscle Contraction

A. Force

1. Number of fibers contracting—more motor units recruited, greater the force

2. Relative size of the muscle—greater cross sectional area, greater the tension possible

3. Series-elastic elements—non-contractile structures of muscles

            a. Movement requires:

i. Moveable structures

ii. Tightening of connective tissue coverings and tendons

b. Tension created at a molecular level is transferred to muscle cell surfaces and through connective tissues that bundle fibers together and ultimately to muscle insertion

c. Internal tension (myofibers) is transferred to external tension (series-elastic elements) to the load

4. Depth of muscle stretch

            a. Optimum resting length is the length at which maximum force can be generated

i. Actin and myosin overlap such that sliding can occur over the entire length of the actin filament

            b. There is also an operational optimum for the whole muscle

                        i. 80% - 120% of normal resting length

B. Velocity and duration

1. Load—as load increases, velocity and duration decrease

2. Muscle fiber type characterized based on:

            a. Speed of contraction—based on efficiency of myosin ATPases

                        i. Slow

                        ii. Fast


            b. Pathway for ATP formation

                        i. Oxidative fibers—aerobic pathways

                        ii. Glycolytic fibers—anaerobic glycolysis

            c. Based on a. and b., three categories

                        i. Slow oxidative fibers

                        ii. Fast oxidative fibers

                        iii. Fast glycolytic fibers


VII. Smooth Muscle

A. Anatomy of smooth muscle fibers

1. Small, spindle-shaped cells

2. Arranged in sheets of opposing fibers

3. Generally two sheets with fibers at right angles to each other

            a. Longitudinal layer—parallel to long axis

            b. Circular layer—around circumference

            c. Alternating contraction of layers—peristalsis

3. Lack highly structured neuromuscular junctions

            a. Varicosities

                        i. Diffuse junctions

4. Lack striations

5. Lower myosin to actin ratio than skeletal (1:13 vs. 1:2)

6. No troponin complex

7. No sarcomeres

            a. Consecutive groups of fibers are organized in a spiral

B. Contraction of smooth muscle

1. Electrical communication between individual smooth muscle cells—gap junctions

            a. Entire sheet responds to a single stimulus

2. Some tissue has pacemaker cells

            a. Some are self-excitatory

3. Overview of process:

            a. Actin and myosin slide (like skeletal)

            b. Rising intracellular Ca2+ triggers contraction

            c. Energized by ATP

4. Difference between smooth and skeletal

a. Ca2+ interacts with regulatory molecules not troponin (do not need to know details)

C. Characteristics of contraction

1. Slow, sustained and resistant to fatigue

2. Energy economy—ATP-efficient contraction

D. Regulation of contraction

1. Multiple neurotransmitters

            a. Different types of nervous innervation with different NT’s

                        i. Sympathetic NS: norepinephrine

                        ii. Parasympathetic NS: ACh

            b. NT’s have different effects

                        i. NE—inhibits contraction

                        ii. ACh—promotes contraction