Cardiac Muscle Structure & Function Flashcards
What are the contractile proteins in the heart muscle?
- Myosin: Two heavy chains and 4 light chains.
- Actin: Similar to skeletal muscle actin; binds tropomyosin and Troponin
List the regulatory proteins
- Troponin C (TN-C)
- Troponin I (TN-I)
- Troponin T (TN-T)
- Tropomyosin
how many Ca2+ binding sites in Troponin C (TN-C)?
Contains only one Ca2+-binding site (unlike skeletal which contains two)
Describe the structure of Troponin I (TN-I)
Contains a unique N-terminal extension of 32 amino acids containing 2 PKA phosphorylation sites critical for adrenergic responsiveness of the heart.
What does Troponin T (TN-T) bind?
Tropomyosin.
What isoform of tropomyosin is found in the heart?
Alpha form
T or F: Myofibrils and mitochondria occupy about 85% of the heart cell volume
True, the rest contains sarcolemma, T-tubules, SR, intercalated disks, gap junctions
T or F: Cardiac muscles are not under direct neural control (unlike skeletal)
True
Contrast cardiac and skeletal muscle cells
Cardiac muscle cells are shorter, narrower & richer in mitochondria than skeletal muscle cells have only one nucleus
T or F: ATPase activity of myosin is slower in cardiac than skeletal
True
What structure provide low resistance pathways for electrical current in myocytes?
Gap junctions
________ connects myocytes to each other.
intercalated discs (Desmosomes provide adhesion)
T or F: coupling between cardiac muscle cells is both mechanical and electrical
True (Gap junctions & intercalated discs/desmosomes)
I band contains what kind of filaments?
Thin filaments
A band contains what kind of filaments?
Thick filaments
How is contraction initiated in a sarcomere?
Contraction is initiated when Ca2+ binds to TnC causing a conformational change in the troponin complex
T or F: myocytes have more SR than skeletal muscle
false, less
T or F: myocytes have bigger T-tubles than skeletal muscle
True
List the sequence of calcium release in cardiac muscle cells
- Depolarization opens the voltage dependent L-type calcium channels leading to Ca2+ influx
- Ca2+ influx triggers release from the SR (CICR) through ryanodine receptors
- Ca2+ increases 10-100 fold
- Contraction is initiated
What mechanism extrude Ca++ from the cytoplasm?
- 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
Briefly describe the contraction-relaxation cycle
- Action potential leads to calcium release.
- Calcium binds to troponin C.
- Troponin complex undergoes structural change, moving 4. tropomyosin out of the way.
- Myosin binds actin and crossbridge moves.
- Calcium is released, tropomyosin reblocks binding site - relaxation
What is the length-tension relationship?
- 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
What law states The Greater the Preload, the greater the force generated
Frank-Starling’s law of the heart
What are the molecular mechanisms behind the length-tension relationship?
- 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.
What is afterload?
the pressure that ventricle has to generate in order to eject blood out of the chamber – most closely related to aortic pressure
What is the most important physiological regulator of contractility?
Norepinephrine, produces a a positive inotropic effect.
What is the Frank-Starling’s law?
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
What is “calcium sensitivity”?
The responsiveness of the myofilament to calcium
What factors regulate calcium sensitivity of the myofilament?
Tn-I phosphorylation
Isoform composition
sarcomere length
T or F: Changes appear to be stoichiometry not changes in isoform switching in HF
False, other way around
What are the 4 major protein changes in HF?
- 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
How is the force-velocity relationship regulated?
Norepinephrine
