Cardiac Muscle Structure & Function

Question 1

What are the contractile proteins in the heart muscle?

Answer 1

• Myosin: Two heavy chains and 4 light chains.

- Actin: Similar to skeletal muscle actin; binds tropomyosin and Troponin

Question 2

List the regulatory proteins

Answer 2

• Troponin C (TN-C)
• Troponin I (TN-I)
• Troponin T (TN-T)
• Tropomyosin

Question 3

how many Ca2+ binding sites in Troponin C (TN-C)?

Answer 3

Contains only one Ca2+-binding site (unlike skeletal which contains two)

Question 4

Describe the structure of Troponin I (TN-I)

Answer 4

Contains a unique N-terminal extension of 32 amino acids containing 2 PKA phosphorylation sites critical for adrenergic responsiveness of the heart.

Question 5

What does Troponin T (TN-T) bind?

Answer 5

Tropomyosin.

Question 6

What isoform of tropomyosin is found in the heart?

Answer 6

Alpha form

Question 7

T or F: Myofibrils and mitochondria occupy about 85% of the heart cell volume

Answer 7

True, the rest contains sarcolemma, T-tubules, SR, intercalated disks, gap junctions

Question 8

T or F: Cardiac muscles are not under direct neural control (unlike skeletal)

Answer 8

True

Question 9

Contrast cardiac and skeletal muscle cells

Answer 9

Cardiac muscle cells are shorter, narrower & richer in mitochondria than skeletal muscle cells have only one nucleus

Question 10

T or F: ATPase activity of myosin is slower in cardiac than skeletal

Answer 10

True

Question 11

What structure provide low resistance pathways for electrical current in myocytes?

Answer 11

Gap junctions

Question 12

________ connects myocytes to each other.

Answer 12

intercalated discs (Desmosomes provide adhesion)

Question 13

T or F: coupling between cardiac muscle cells is both mechanical and electrical

Answer 13

True (Gap junctions & intercalated discs/desmosomes)

Question 14

I band contains what kind of filaments?

Answer 14

Thin filaments

Question 15

A band contains what kind of filaments?

Answer 15

Thick filaments

Question 16

How is contraction initiated in a sarcomere?

Answer 16

Contraction is initiated when Ca2+ binds to TnC causing a conformational change in the troponin complex

Question 17

T or F: myocytes have more SR than skeletal muscle

Answer 17

false, less

Question 18

T or F: myocytes have bigger T-tubles than skeletal muscle

Answer 18

True

Question 19

List the sequence of calcium release in cardiac muscle cells

Answer 19

1. Depolarization opens the voltage dependent L-type calcium channels leading to Ca2+ influx
2. Ca2+ influx triggers release from the SR (CICR) through ryanodine receptors
3. Ca2+ increases 10-100 fold
4. Contraction is initiated

Question 20

What mechanism extrude Ca++ from the cytoplasm?

Answer 20

• SR Ca2+-ATPase (SERCA); 90% in rodents; 70% in humans
• Sarcolemmal Na+-Ca2+ exchanger (NCX); 28% in humans
• PMCA & mitochondrial Ca2+ uniporter (~2% in all species

Question 21

Briefly describe the contraction-relaxation cycle

Answer 21

1. Action potential leads to calcium release.
2. Calcium binds to troponin C.
3. Troponin complex undergoes structural change, moving 4. tropomyosin out of the way.
4. Myosin binds actin and crossbridge moves.
5. Calcium is released, tropomyosin reblocks binding site - relaxation

Question 22

What is the length-tension relationship?

Answer 22

• contraction at low sarcomere resting lengths= small amount of active tension developed
• contraction at increased sarcomere resting lengths= dramatic increase in amount of active tension developed

Question 23

What law states The Greater the Preload, the greater the force generated

Answer 23

Frank-Starling’s law of the heart

Question 24

What are the molecular mechanisms behind the length-tension relationship?

Answer 24

• Extent of overlap: the changes in the resting length of the whole muscle are associated with proportional changes in the individual sarcomere. Peak tension development occurs at sarcomere lengths of 2.2 to 2.3 mM.
• Change in the sensitivity of the myofilament to calcium: At longer lengths, more of the cross-bridges become activated by the same change in intracellular calcium.
• Increased calcium release: Occurs several minutes after changing the length of the muscle.

Question 25

What is afterload?

Answer 25

the pressure that ventricle has to generate in order to eject blood out of the chamber – most closely related to aortic pressure

Question 26

What is the most important physiological regulator of contractility?

Answer 26

Norepinephrine, produces a a positive inotropic effect.

Question 27

What is the Frank-Starling’s law?

Answer 27

the greater the volume of blood entering the heart during diastole, the greater the volume of blood ejected during contraction , due to the length-tension relationship

Question 28

What is “calcium sensitivity”?

Answer 28

The responsiveness of the myofilament to calcium

Question 29

What factors regulate calcium sensitivity of the myofilament?

Answer 29

Tn-I phosphorylation
Isoform composition
sarcomere length

Question 30

T or F: Changes appear to be stoichiometry not changes in isoform switching in HF

Answer 30

False, other way around

Question 31

What are the 4 major protein changes in HF?

Answer 31

• TnT: more fetal pattern, no effect on motility or force generation in vitro
• Myosin heavy chain: Increased b-MHC, associated with lower ATPase and reduced ventricular contractility.
• MLC: Atrial isoform switching in ventricles, temporally correlated to progression to failure.
• Titin: Increase in N2BA isoform (more compliant than the N2B isoform), associated with reduced myocardial stiffness

Question 32

How is the force-velocity relationship regulated?

Answer 32

Norepinephrine