Cardiac Muscle Structure & Function Flashcards Preview

CVPR Exam 1 > Cardiac Muscle Structure & Function > Flashcards

Flashcards in Cardiac Muscle Structure & Function Deck (42):
1

What general role does the heart play in the CV system?


• Simple pump whose sole job is to match cardiac output to the demands of the body
• CO = stroke volume * heart rate

2

What is meant by the term myofibril?

• End to end arrays of identical sarcomeres

3

What is meant by the term sarcomere?

• Unit of contractile activity composed mainly of actin and myosin and extending from Z line to Z line in a myofibril

4

What is meant by the term myocyte?

• Single muscle cells containing all the usuall cell organelles plus many myofibrils

5

What is meant by the term "muscle"?

• Organized array of muscle fibers

6

What are the special features of the cardiac muscle tissue?

• Autonomic innervation
• Composed of interconnected mono-nucleated cells imbedded in a weave of collagen
• Much longer reploarization thatn skelatal muscle
• ATPase activity is slower than skelatal muscle
• Thin filament regulation of contraction
○ Not thick filament regulation in smooth muscle
• Coupling between cells is both mechanical and electrical
• Very rich in mitochondria
○ 85% of a cardiac myocyte is myofibril and mitochondria

7

What factors go together to determine stroke volume?

• Preload, afterload, contractility

8

What is the relationship that determines Cardiac Output?

• CO = stroke volume * heart rate

9

What are the proteins involved in the contractile unit of the cardiac myocyte?






• Myosin
• Actin
• Thin filament regulatory proteins
○ TN-C
○ TN-I
○ TN-T
○ TM

10

What is the cross-bridge cycle?

• Cardiac contraction is a series of interactions between Calcium, the regulatory proteins and th eactomyosin system
• In resting muscle, at low intercellular calcium, the TN-TM complex inhibits the actin-myosin combination and with an increase in the myoplasmic Calcium, TN relaeases it's inhibiton, moving TM out of the actin groove, allowing myosin to bind
• Myosin heads undergo a power-stroke, and myolfilaments shorten

11

What are the different Troponins and what do they do?

• Thin filament binding proteins
○ TN-C - contains only one Ca2+ binding site
○ TN-I - contains a unique N-terminal extension of 32 amino acids which is highly regulated by phosphorylation
§ PKA sites
○ TN-T - isoforms are developmentally and pathologicall rugulated
§ Unique N-terminal extension is involved in regulation fo calcium sensitivity

12

What is Actin?

• Similar to skelatal muscle actin
• Binds tropomyosin and Troponin

13

What is myosin?

• One of the contractile proteins in a cardiac myocyte
• Two heavy chains and 4 light chains
• Developmental and pathophysiological regulation of isoform composition exists

14

What is titin and what does it do?


• Very large protein
• Funcitons as an elastic spring
• Largely responsible for resting tension of cardiac myocyte
• N2B and N2Ba are two major isoforms

15

What are some examples of pathological changes that affect the Frank-starling Law?

• Frank-starling law deals with the length-tension relationship of the cardiac myocyte that explains increased preload meaning increased stroke volume
• Cardiac titin isoform is too stiff
○ Low compliance leads to decreased preload)
• Calcium sensitivity of the myofilaments increases as sarcomeres are stretched
○ Same calcium but greater force of contraction
• Closer lattice spacing
○ Stretched sarcomeres have altered spacing between activn and myosin
○ More force generated per crossbridge or changes in cooperativity

16

What three factors at the cellular level will influence the length-tension relationship?

• Overlap of thick and thin filaments
• Changes in calcium sensitivity
• Increased calcium release

17

What is the Frank-Starling Law?

• Stroke volume of the heart increases in response to an increase in the volume of blood filling the heart
○ "preload" or end diastolic volume
• As long as all other factors are constant an incrased preload will result in an increased stroke volume
• At the cellular level this is demonstrated by the length-tension relationship
○ Overlap of thick and thin filaments
○ Changes in calcium sensitivity
○ Increased calcium release

18

What are the differences between the two major isoforms of titin?

• N2B - stiffer isoform
• N2Ba - not as stiff isoform

19

What are the three general regulators of stroke volume?



• Preload
• Afterload
• Contractility

20

When you see Frank-Starling law you think…?

• Pre-load, as part of stroke volume
• In particular, the length-tension relationship at the cardiac myocyte level that determines pre-load

21

What goes into Pre-load?

• The molecular basis for changin Pre-load goes into the Length-Tension relationship (Frank-Starling law)
• The lower the preload, the lower the active tension. The higher the preload, the higher the active tension

22

What is meant by afterload?







• Most closely associated with aortic (systemic) pressure
• Afterload can also be described as the pressure that a ventricle has to generate to ejet blood out of the chamber
• Has to do with the Force-velocity relationship
○ The greater the afterload (force that ventricle has to exert) the lower the shortening velocity
• Shortening velocity is inversely proportional to afterload

23

What Law can be used to describe the greater force needed to eject a greater ventricular volume?

• Law of Laplace
○ T = P * r/h
○ R- radius
○ P- pressure
○ H- wall thickness

24

What must happen to eject an increased ventricular volume?

• Increased force of an individual muscle cell
• Must overcome increased intraventricular pressure

25

At any given volume, what happens when you increase the tension of the individual myocyte?

• Increases the intraventricular pressure

26

What does an increase in ventricular volume mean for the Frank-Starling Law?

• Increase in volume means increase in diamter, which stretches all the cells
• Results in overall increase of cardiac myocyte length
• Increases active tension

27

What is meant by ionotrope?

• Substances that change contracility are ionotropes
○ Can be negative or positive ionotrope

28

What is meant by contractility?

• Force with which the heart contracts
• Most important physiological regulator is norepinephrine
• Substances that change contracility are ionotropes
○ Can be negative or positive ionotrope

29

Hypertrophy can lead to what change that can result in what heart disease?



• Hypertrophy can, by altering calcium sensitivity, mess with contractility

30

What are the two main mechanisms of altering contractility?

• Translational changes
○ Sarcomeric proteins (upregulation of fetal proteins)
○ Changes in signaling proteins
• Post-translational changes of sarcomeric proteins
○ Possible phosphofingerprint of cardiac disease?

31

What levels of cardiac funciton are affected in disease?

• Organ level
• Fiber level
• Cellular level
• Myofibrillar level

32

What problem with heart contraction does dilation cause?

• Changes in contractility
○ Specifically thorugh changes in force output (maximal)

33

How do cardiac myocytes facilitate cell-cell communication?



• Intercalated discs
○ Coincide with Z discs
○ Contain desomosomes and gap juncitons
○ Desomosomes provide adhesion and assure that he force generated in one cell is carred to other (ECM)
○ Gap junctions provide low resistance pathways for electrical current conduction

34

What do desmosomes do for cardiac myocytes?

• Desomosomes provide adhesion and assure that he force generated in one cell is carred to other (ECM)

35

What do gap junctions do for the cardiac myocytes?

• Gap junctions provide low resistance pathways for electrical current conduction

36

What degree of overlap has peak tension development?

• 2.2 to 2.3um

37

What factors regulate calcium sensitivity of the myofilament?

• TN-I phosphorylation
• TN-T isoform composition
• Sarcomere length

38

What does the N-terminal extension of TN-T do?

• Decreases the calcium sensitivity of the myofilament

39

What does PKA phosphorylation of TN-I do?

• Decreases the calcium sensitivity of the myofilament

40

What changes the shortening velocity on the sarcomeric level?

• Phosphorylation of MLC
• Phosphorylation of MyBPC

41

What is meant by positive ionotropic effect?

• Any intervention that increases the peak isometric tension that a muscle can develop at a fixed length

42

When you think norepinephrine you think

• The most important physiological regulator of contractility