(Dr. Critz) Lecture 5 Striated Muscle and Excitation-Contraction Coupling

Question 1

Describe the organization of muscle fiber and a single myofibril.

Answer 1

Muscle fibers contain single multinucleate cells, are bounded by sarcolemma and contain myofibrils.
A myofibril contain actin and myosin filaments, and is invested with sarcoplasm, mitochondria, and sarcoplasmic reticulum

Question 2

What is the role of titin in the myofibril, describe its size, and what is another name for it?

Answer 2

Titin (connectin) forms the attachment of myosin to the Z disc and the M line. It behaves as a “spring” to provide elasticity, and closer to the M line, titin acts as a scaffold, or a support filament for myosin. It is the largest polypeptide in the human body (~35k amino acids)

Question 3

What protein are the I band and A band made of, and how do the I band and A band change in size during contraction?

Answer 3

The I band (thin filament) is made of actin and shortens upon contraction. The A band (thick filament) is made of myosin and has constant length during contraction.

Question 4

Describe sliding filament mechanism.

Answer 4

Tropomyosin blocks the actin active site, preventing binding onto myosin heads -> Ca2+ binds to troponin, moving tropomyosin -> myosin heads can bind onto actin because tropomyosin has moved away from the actin binding site -> myosin moves, actin generates tension, contraction in muscle; myosin pulls actin toward M-line, myosin moves toward Z-line

Question 5

What are three components of the troponin complex and what are their roles in the sliding filament theory?

Answer 5

Troponin I binds actin
Troponin T binds tropomyosin
Troponin C binds Ca2+

Question 6

Describe the structure and list the components of actin filaments.

Answer 6

The backbone of the actin filament is a double-stranded F-actin protein molecule, with both strands wound into a helix. Each strand is composed of polymerized G-actin, each with MW ~42K. Each G actin has an ADP attached, believed to be the active sites on with which cross bridges of myosin filaments interact to cause muscle contraction.

Question 7

What is the approximate distance between active sites on actin filaments?

Answer 7

~2.7 nm

Question 8

Describe the myosin filament and the myosin molecule

Answer 8

The myosin molecule is ~480K MW, containing 2 heavy chains (200,000 kD), and 4 light chains (20,000 kD), as well as an ATPase in the head region for cross-bridge formation. There are ~200 myosin molecules per filament, and each filament is ~1.6 um wide.

Question 9

What causes rigor mortis?

Answer 9

Contracture due to loss of ATP, so myosin head remains bound to the actin active site, and stays locked in place

Question 10

Describe the power stroke portion of the sliding filament mechanism

Answer 10

The myosin head is initially bound to active site with ADP associated, then ADP is exchanged for ATP. The ATP is hydrolyzed, which releases the myosin head.

Question 11

Describe the speed of contraction between white and red skeletal muscle their Type names, and what determines their speed of contraction.

Answer 11

White muscle (type II) is fast, and red muscle is slow (type I). The speed of contraction is determined by the Vmax of myosin ATPase. So white muscle contains greater amount of ATPase.

Question 12

What are the structural differences between fast fibers and slow fibers?

Answer 12

Fast fibers (Type II) are glycolytic, have large diameter, low myoglobin, low capillary density, and few mitochondria.
Slow fibers (Type I) are oxidative (low glycolytic enzymes), have a small diameter, high myoglobin, high capillary density, and abundant mitochondria.

Question 13

Is there a way to change someone’s ratio of fast to slow fibers?

Answer 13

No, the ratio is fixed, as it is genetically determined, and does not change with training.

Question 14

In what order are slow and fast skeletal muscle fibers activated?

Answer 14

Slow fibers are activated first, and fast fibers are recruited when more force is needed.

Question 15

Compare the innervation of the smallest motor units with large motor units, and how their innervation relates to their function.

Answer 15

The smallest motor units (larynx, extraocular eye muscle) are richly innervated, with 2-10 fibers/unit, allowing for fine control and rapid response.
Large motor units (e.g. soleus muscle) are coarsely innervated, with 200-300 fibers/unit for coarser control and slow response.

Question 16

Describe “measured force,” and how it relates to motor units.

Answer 16

Overlap of motor units provides “measured force” is the ability to estimate how heavy something is, and allows recruitment of the proper amount of motor units.

Question 17

What is force summation and what contributes to it?

Answer 17

Force summation is the additive increase in tension as stimulus intensity increases resulting from:

1. Increasing the number of motor units- size principle
2. Increasing stimulation frequency

Question 18

What is the size principle and what is its significance?

Answer 18

Motor units recruit from smallest to largest fibers which allows graded force generation; the smaller motor units are driven by small motor nerve fibers, and the small motoneurons in the spinal cord are more excitable than the larger ones, so naturally they are excited first.

Question 19

What is the basis of selectivity of the nicotinic acetylcholine receptor (nACHR), and how does it compare to that of the voltag-gated Na+ channel?

Answer 19

The nAChR basis of selectivity is a ring of charges, much simpler/less strict than the tight filter of voltage-gated Na+ channels

Question 20

Describe excitation-contraction coupling in skeletal muscle.

Answer 20

1. An action potential in the transverse tubule causes a conformational change in the voltage-sensing DHP receptors, opening the Ca2+ release channels in the terminal cisternae of the SR (ryanodine receptors), and permitting Ca2+ to rapidly diffuse into the sarcoplasm and initiate muscle contraction.
   Ca2+ is pumped back into SR via Ca2+ ATPase.
   Storage by calsequestion in SR terminates contraction.

Question 21

What molecular class does amlodipine belong to, and by what mechanism does it treat hypertension?

Answer 21

Amlodipine is a dihydropyridine; when it binds to DHP receptors (an isoform of VG Ca2+ channels, Cav1.1), which are mechanically coupled to ryanodine receptors in skeletal muscle, it prevents influx of Ca2+ into cardiac smooth muscle.

Question 22

Describe the differences in the pharmacology and clinical use of curare and botulinum toxin

Answer 22

Curare competitively blocks POSTsynaptic ACh binding site, reduces EPP and blocks AP, leading to paralysis and respiratory arrest. It is clinically used for surgery.
Botulinum toxin blocks presynaptic ACh release, reduces EPP and blocks AP. It causes paralysis, and is clinically used for dystonia and to reduces wrinkles.

Question 23

Describe the pathophysiology of Lambert-Eaton Myasthenic Syndrome, and treatment.

Answer 23

LEMS is an autoimmune disease which attacks voltage gated Ca2+ channels in presynaptic motor neuron terminals. LEMS diminishes EPP amplitude and causes muscle weakness and paralysis. LEMS is treated with acetylcholinesterase (AChE) inhibitors, to increased ACh content in the synaptic cleft.

Question 24

Phosphocreatine maintains contraction for how long?

Answer 24

5-8 seconds

Question 25

Glycolysis generates ATP and phosphocreatine. How long is muscle contraction maintazined?

Answer 25

1 minute

Question 26

Oxidative phosphorylation provides how much (%) of energy required for muscle contraction?

Answer 26

~95%

Question 27

Short-term metabolism lasts up to 4 hours and longer-term metabolism is defined as anything past the 4 hours. What do each of these metabolism period run off of?

Answer 27

Short-term: 50% carbohydrates, 50% available fat

Longer-term: from stored fat metabolism

Question 28

What is a fused tetanis?

Answer 28

When there is very high Ca2+ and no more force can be generated