Week 1: Physiology of skeletal muscle

Question 1

What is the difference between Type I and Type II muscle fibers?

Answer 1

Type I=red fibers
-abundance of mitochondria
-slow twitch response
-aerobic metabolism
-more resistant to fatigue
-efficient for sustained forces
Type II=white fibers
-relatively depleted of mitochondria
-glycolysis
-fast twitch response
-fatigue easily
-efficient for quick, intermittent movements

Question 2

Name the major protein components of the thick and thin filaments.

Answer 2

Thick filaments
-myosin, body of thick filament made of hundreds of myosin tails packed together
Thin filaments
-actin, tropomyosin, and troponin (subunits C, I, T)
-Tropomyosin lies in grooves between two actin polymers, lies along length of ~7 actin monomers
-troponin C binds Ca2+ which initiates muscle contraction

Question 3

Explain the sliding filament model of muscle contraction, including the relationship between cross bridge formation, force generation, and ATP hydrolysis

Answer 3

• During contraction, thick and thin filaments slide past each other, increasing overlap
• myosin heads on thick filaments form cross bridges with actin on thin filaments (attach at 90 degrees and swivel to 45 degrees to pull thin filaments)
• total force exerted by muscle proportional to number of cross bridges between filaments
• requires hydrolysis of ATP by myosin ATPase, its activity is activated 100 fold by binding of actin to myosin (release of ADP & P is rate limiting step)
• myosin ATPase is slow in red fibers, fast in white fibers

Question 4

Describe the role of calcium in the regulation of skeletal muscle contraction

Answer 4

• when calcium is low: troponin and tropomyosin blocks actin activation of myosin ATPase
• elevation of Ca2+: binds to Troponin C, causes conformation change in other troponin subunits, induces tropomyosin molecule from one position on actin to another–>assoc. with activation of myosin ATPase by actin
• steric blocking model:
• tropomyosin molecule at original position with low Ca2+ levels physical blocks site of attachment of myosin and actin, preventing contraction and myosin ATPase activity
• Release of ADP and P from myosin ATPase generates force (bending of myosin head)
• addition of ATP causes myosin to be in a low actin affinity state, causes release of myosin from actin. Without ATP–>rigor mortis

Question 5

Distinguish between isotonic and isometric contractions

Answer 5

Isotonic contraction=contractions resulting in a change in muscle length
-concentric contraction-muscle shortens
-eccentric contraction-increase in muscle length
Isometric contraction=contractions that cause no change in muscle length

Question 6

Describe the force- velocity relationship for isotonic contraction

Answer 6

As size of the load increases:

• rate of muscle shortening decreases (velocity)
• extent of muscle shortening and duration of contraction also decreases
• Power (force x velocity) increases to its maximum at 1/3 of max load, then decreases

Question 7

Explain the length tension curve for an isometric contraction

Answer 7

• skeletal muscle operates in narrow range near the optimum length for active force generation (since confined to attachment to skeleton)
• passive tension (resistive force) increases with increased muscle length
• active tension (Ca dependent) also depends on muscle length (bell curve), is determined from total tension-passive tension since it can’t be measured directly

Question 8

Describe the mechanism whereby force of contraction can be increased by increasing the frequency of motor nerve firing.

Answer 8

• action potential is short compared to duration of twitch (5msec vs 10-100msec)
• absolute refractory period is very short
• can generate a second action potential before muscle has relaxed
• when that happens, additional force can be generated b/c free cytoplasmic Ca2+ is still high, and 2nd stimulus releases more Ca2+ from SER to cytoplasm–>results in increased force of contraction
• however increases in stimulation above a certain point, individual twitches fuse, and sum to yield max tension (=tetanus tension)
• increases in stimulation above this frequency produce no further increases in tension

Question 9

What causes malignant hyperthermia?

Answer 9

• mutations in ryanodine receptor (SR Ca release channel) causes Ca ions to leak out of SR into cytoplasm
• causes sustained muscle contraction
• CA-ATPase tries to pump Ca ions back into SR, but they just leak out, causes large utilization of ATP with associated release of heat

Question 10

What is the cause of muscular dystrophy?

Answer 10

-absence or mutation of dystrophin, which links cytoskeleton to other integral membrane proteins

Question 11

Describe the mechanism whereby force of contraction can be increased by recruitment of different sizes of motor units.

Answer 11

Contractile force can be increased by recruiting more motor units

• A motor unit consists of one somatic efferent (motor) neuron and all of the muscle fibers (cells) that it innervates.
• First recruit small motor units: slow conduction, relatively excitable, frequently active
• Then recruit large motor unit: fast conduction, relatively unexcitable, recruited infrequently in forceful contraction

Question 12

List the mechanism/cause of the following diseases: hypokalemic periodic paralysis, hyperkalemic periodic paralysis, paramyotonia congenita, myotonia congenita

Answer 12

1. hypokalemic periodic paralysis: Mutations in the voltage sensor of the channels; reduced (50%) Ca influx
2. hyperkalemic PP: mutations prevent normal fast inactivation of Na channels, Sustained depolarization/block of action potentials and muscle weakness or myotonia
3. Paramyotonia congenita: cold activated. Decreased rate of inactivation, increased rate of recovery from inactivation -> sustained depolarization -> repetitive firing of action potentials
4. myotonia congenita: Reduced Cl conductance leads to delayed repolarization, and a state of hyper excitability