Cardiac Muscle Structure & Function

Question 1

Composition of contractile protein

Answer 1

• myosin: 2 heavy chains, 4 light chains
• actin: similar to skeletal muscle actin; binds tropomyosin and troponin
• thin filament regulatory proteins:
  i. TN-C: one Ca2+ binding site
  ii. TH-I: N-terminal regulated by phosporylation (PK sites)
  iii. TN-T: Isoforms are developmentally & pathologically regulated
  iv. TM: only alpha isoform

Question 2

Cardiac muscle structure

Answer 2

• interconnected mono-nucleated cells w/in collagen
• cells w/large number of myofibrils
• majority of cell volume=mitochondria
• cells coupled both electrically and mechanically

Question 3

Regulation of calcium flow w/in muscle cells

Answer 3

1. depolarization –> L-type channels open –> calcium influx
2. calcium influx –> calcium release from SR via ryanodine receptors (CICR)
3. calcium binding to TN-C triggers contraction
4. calcium removed by SR Ca2+-ATPase

Question 4

Cross-bridge cycle of cardiac muscle contraction

Answer 4

• @ rest: low intracell Ca2+ –> TN-TM complex inhibits actin-myosin combination
• increase myoplasmic Ca2+: TN releases inhibition, moves TM out of actin groove, myosin binds –> myosin head undergoes power stroke –> myofilaments shorten

Question 5

Cardiac output=

Answer 5

Stroke volume x heart rate

Question 6

Regulators of stroke volume

Answer 6

• pre-load
• afterload
• contractility

Question 7

Molecular mechanism of length-tension relationship

Answer 7

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Question 8

Pre-load effects on stroke volume

Answer 8

• based on length-tension relationship –>
• stimulating contraction at low lengths (i.e. when heart chamber is empty) generates less tension when stimulated at increased muscle lengths (i.e. when heart chambers are full)

Question 9

Afterload effects on stroke volume

Answer 9

• related to aortic (systemic) pressure
• pressure ventricles need to generate to eject blood from chamber
• inverse relationship between shortening velocity and afterload

Question 10

Contractility definition/effects on stroke volume

Answer 10

• force w/which heart contracts
• regulated by norepinerphine
• “ionotropes” (positive or negative) change contractility

Question 11

Frank-Starling Law

Answer 11

• stroke volume of heart increases in response to an increase in the volume of blood filling the heart (=end diastolic volume)
• i.e. increase in pre-load = increase in stroke volume

Question 12

Factors that may contribute to Starlings Law

Answer 12

1. Cardiac titin isoform is very stiff
2. Ca2+-sensitivity of myofilaments increases as sarcomeres are stretched
3. closer lattice spacing: stretched sarcomeres have altered spacing between actin and myosin

Question 13

Hypertrophy impact on cardiac muscle

Answer 13

1. cell growth:
   i. concentric
   ii. upregulation of fetal gene program
2. changes in contractility (mainly calcium sensitivity)

Question 14

Dilation impact on cardiac muscle

Answer 14

1. cell growth:
   i. eccentric
   ii. upregulation of fetal gene program
2. changes in contractility: changes in force output (maximal)

Question 15

Mechanism of changes in contractility

Answer 15

1. translational changes:
   i. sarcomeric proteins (upregulation of fetal proteins)
   ii. changes in signaling proteins
2. post-translational changes of sarcomeric proteins