Muscle I and II

Question 1

What is the name of the conventional myosin in muscle? What is its specific structure? What do its pieces contain?

Answer 1

Muscle myosin II. It is a hexamer with 2 heavy chains and 2 pairs of light chains. The heavy chain portion contains actin and the ATP binding site. (can only bind strongly to one or the other, but not both)

Question 2

How many different types of myosin are there?

Answer 2

10 types

Question 3

What is titin made out of? size? Is it motor, regulatory, or structural? What is its purpose during myogenesis? What type of tension is it responsible for?

Answer 3

Very large elastic protein. Structural. Serves as a molecular ruler during myogenesis. Responsible for passive length tension.

Question 4

Is nebulin motor, regulatory, or structural? what type of muscle is it found in? What type of protein is it? How many per actin?

Answer 4

Structural. Found in skeletal muscle only. Long inelastic protein. 2 per actin.

Question 5

What are the 4 regulatory proteins in muscle? What do they do?

Answer 5

All part of the troponin complex, except the last one.
Troponin-T: binds to tropomyosin and helps position it on the actin, which exposes the myosin-binding sites.
Troponin-I: binds to actin and prevents myosin from binding to it
Troponin-C: calcium binds to it causing a conformational change that disrupts the actin-TnI interaction
Caldesmon/Calponin: Smooth muscle only. acts similar to TnT and TnI

Question 6

Explain the length-tension relationship: what if the fiber is too long/short?

Answer 6

Too long: Not enough cross bridge can form leading to less tension and force.
Too short: Thick filament clashes w/z disc leading to less tension and force.
optimal length of sarcomere: 2-2.25 micrometers

Question 7

1. is Type I muscle slow or fast twitch? How does it fatigue?
2. Myoglobin color? metabolism type?
3. Mitochondria and glycogen levels?
4. size?

Answer 7

1. Slow twitch, fatigue resistant
2. Red myoglobin, oxidative metabolism
3. High mitochondria, low glycogen
4. small

Question 8

1. is Type IIa muscle slow or fast twitch? How does it fatigue?
2. Myoglobin color? metabolism type?
3. Mitochondria and glycogen levels?
4. size?

Answer 8

1. fast twitch, fatigue resistant
2. red myoglobin, oxidative metabolism
3. High mitochondria, abundant glycogen
4. intermediate size

Question 9

1. is Type IIb/IIx muscle slow or fast twitch? How does it fatigue?
2. Myoglobin color? metabolism type?
3. Mitochondria and glycogen levels?
4. size?

Answer 9

1. fast twitch, fatiguable
2. white myoglobin, glycolytic metabolism
3. Fewer mitochondria, high glycogen
4. Large in size

Question 10

What does endurance training do to muscles?

Answer 10

Increase in type IIa fibers, mitochondria, and myoglobin. Decrease in type IIx fibers.

Question 11

explain the L-type calcium channel, and what it causes to happen, all the way to troponin C

Answer 11

end plate potential turns into an action potential and then travels down t tubules where it activates the L-type calcium channels (DHP receptors). It then mechanically reacts with the ryanodine receptor RyR-1 to make Ca++ be released from the sarcoplasmic reticulum. The calcium binds to troponin C to increase Pi dissociation

Question 12

In cardiac muscle instead of coupling with a ryanodine receptor, what happens?

Answer 12

calcium-induced calcium release with ryanodine receptor Ryr-2.

Question 13

How does nore affect cardiac muscle?

Answer 13

it binds to beta andrenergenic receptors which increases Ca++ influx due to phosphorylation of Ca++ channels. Then you have calcium induced calcium release.

Question 14

What does an overall increase in calcium due to heart contraxtion and relaxation

Answer 14

increased HR, contractility (inotrophy), and relaxation rate (lusitrophy). More rapid with more force.

Question 15

Explain what calcium does in smooth muscle for thick filaments — Calcium DEPENDENT

Answer 15

For thick filaments:

1. Calcium binds to calmodulin
2. calcium calmodulin complex activates MLCK, which phosphorylates myosin light chain and allows it to interact with actin.
3. The myosin light chain can stay in the phosphorylated state for a prolonged period of time forming myosin cross bridges (latch bridges) thus keeping smooth muscle tonically active.
4. Myosin goes back to relaxed state once MLCP dephosphorylates the light chain. (MCCP can be activated by cGMP).

Question 16

Explain what calcium does with thin filaments?

Answer 16

Calcium binds to caldesmon and calponin exposing tropomyosin and allowing MCL to bind to it. Caldesmon is similar to TnT and TnI in striated muscle.

Question 17

What is Familial Hypertrophic Cardiomyopathy (HCM)

Answer 17

Leading cause of SCD. HCM is usually caused by a single amino acid mutation in the cardiac myosin heavy chain. The mutation changes ATP hydrolysis in the myosin which decreases force production leading to ventricular wall hypertrophy.

Question 18

What is malignant hyperthermia?

Answer 18

autosomal inherited myopathy due to defect in skeletal muscle ryanodine receptors Ryr-1. Characterized by uncontrolled muscle contracture and hyperthermia.

Question 19

What is cardiac hypertrophy and failure?

Answer 19

caused by reduction in cardiac muscle ryanodine receptors Ryr-2.

Question 20

What does Viagra do?

Answer 20

inhibits cellular breakdown of cGMP by blocking PDE5 and so enhances the effect of NO/cGMP, which causes the relaxation of smooth muscle. the localized relaxation of smooth muscle allows blood to swell in corpus cavernosum.

Question 21

What proteins help Ach vesicles fuse with membrane to enter the synaptic cleft?

Answer 21

SNARE proteins.

Question 22

The nicotinic-Ach receptor is what type of channel?

Answer 22

A ligand-gated sodium channel.

Question 23

In skeletal muscle, the L-type Ca++ channel (DHP) receptor let’s calcium flow in, in skeletal muscle.

Answer 23

False. Although called a calcium channel, in skeletal muscle calcium doesn’t actually flow through.

Question 24

What is myasthenia gravis? Involves what channel?

Answer 24

Blocking Ach receptors by AchR antibodies in the synapse.

Question 25

Difference between multi-unit and single unit smooth muscle?

Answer 25

multi-unit- each fiber can contract independently of others. Controlled independently by nerves. single-unit- Aka visceral smooth muscle. Tight contact with gap-junctions.

Question 26

What is different about the DHP receptor in smooth muscle?

Answer 26

A TRUE voltage-gated Ca++ channel

Question 27

Instead of neuromuscular junctions, the ANS communicates with smooth muscle how? Via what?

Answer 27

autonomic nerves branch out onto the surface of smooth muscle and release neurotransmitters via varicocities.

Question 28

Smooth muscle: sympathetic NS uses what neurotransmitters and what receptor? Explain what happens depending on the receptor. Cardiac muscle: B-adrengergenic receptor with nore does what?

Answer 28

epi/nore, onto alpha or beta adrenergenic receptors. alpha--- G alpha(q) uses IP3 DAG pathway to ACTIVATE SMOOTH MUSCLE CONTRACTION Beta--- G alpha(s) uses adenylate cyclase and cAMP pathway to INHIBIT CONTRACTION. For cardiac Beta-receptor with nore, it increases HR (opposite of the smooth muscle)

Question 29

Smooth muscle: parasympathetic NS uses what neurotransmitter and what receptor? What is the overall effect?

Answer 29

G (alpha-q) protein. Uses Ach onto muscarinic receptors. uses Phospholipase C, IP3 DAG pathway to ACTIVATE SMOOTH MUSCLE CONTRACTION.

Question 30

Nitric oxide is what type of hormone? Produced by what? What pathway does it use, and what is the effect? What drug helps it?

Answer 30

Paracrine hormone produced by endothelial cells. Diffuses to nearby smooth muscle, using guanylate cyclase cGMP to inhibit Ca influx, resulting in RELAXATION OF SMOOTH MUSCLE. Viagra encourages this process.

Question 31

Explain calcium-independent contraction of smooth muscle.

Answer 31

Rho-Kinase cascade leads to phosphorylation of myosin light chain phosphatase, an enzyme that removes a phosphate from the myosin light chain. This deactivates this phosphatase, leaving it in an active phosphorylated state, which INCREASES contraction of smooth muscle.

Question 32

What do stretch receptors initiate? Important in what?

Answer 32

an intracellular cascade leading to calcium influx. Important in peristalsis.

Question 33

Explain spontaneous contraction of smooth muscle

Answer 33

In stomach, smooth muscle receives spontaneous "slow waves" from interstitial cells of Cajal (ICC) that result in action potentials when threshold is reached.

Question 34

More potassium leak channels open means what for smooth muscle? What does 4-AP do?

Answer 34

More hyperpolarized the cell will be, and thus voltage-gated Ca++ channels will be closed. 4-AP is a potassium channel blocker. Results in membrane depolarization, and the opening of voltage gated calcium channels.

Question 35

What do catecholamines do in the heart?

Answer 35

activate intracellular cascades that lead to phosphorylation/activation of enzymes involved in heart rate, contractility, relaxation, and conduction speed (dromotropy).

Question 36

What effect does catecholamine have on phospholamban?

Answer 36

Phospholamban normally inhibits the SERCA pump, but is phosphorylated in response to catecholamine administration. Thus, SERCA activity increases, and cardiac muscle relaxes. However, this increases Ca++ concentration in the sarcoplasmic reticulum, so you get increased contractility upon stimulation.

Question 37

in endothelial cells, an increase in calcium does what? | In contrast, an increase in calcium in smooth muscle does what?

Answer 37

vasodilation, due to nitric oxide production. | in smooth muscle, it's vasoconstriction.

Question 38

resting potential of smooth muscle?

Answer 38

-50 to -60 mv

Question 39

The delayed onset and prolonged contraction of smooth muscle is due to what?

Answer 39

Slower cycling rate of smooth m. myosin cross-bridge formation. However, it is strong (lots of bridges)

Question 40

An endplate potential occurs at the NMJ due to what fact? Think channels.

Answer 40

sodium permeability becomes much greater than potassium permeability. (NMJ channels are LIGAND gated, not voltage gated)

Question 41

What does BOTOX do?

Answer 41

Ach release blocker. Inhibition of vesicular fusion by inhibition of SNARE proteins.

Question 42

Calcium INDEPENDENT contraction of smooth muscle?

Answer 42

The intracellular signaling of the RhoA "Rho Kinase Cascade." 1. The activated RhoA kinase phosphorylates MLCP, which usually removes a phosphate from MLC. Instead, it gets its phosphate from RhoA so it is deactivated 2. MLC is phosphorylated because it isn't inhibited, so it can keep the smooth muscle contracted.