Excitation-Contraction Coupling -February 13

Question 1

Comparison structure contractile filaments in cardiac and skeletal muscles (4)

Answer 1

• sarcoplasmic reticulum smaller in cardiac
• t-tubules larger in diameter in cardiac and penetrate into the cell along z-line
• longitudinal elements of tubule system in cardiac
• 40% of cell volume occupied by mitochondria (cell almost exclusive dependence on oxygen metabolism)

Question 2

Location excitation-contraction coupling in cardiac fibers

Answer 2

• where the sarcoplasmic retculum comes into close physical contact with T-tubules (occurs in numerous places along sarcoplasmic reticulum)
  i. e. dyad

Question 3

Steps to contraction in cardiac fibers

Answer 3

1. Ca2+ enters the cell through voltage gated Ca2+ channels during the plateau phase of the action potential
   2 Ca2+ spreads through the myoplasm and raises intracellular calcium concentration from its resting level to 100 nM to 300nM
   (insufficient to produce a contraction forceful enough to maintain CO)
2. BUT Ryanodine receptors are sensitive to myoplasmic Ca2+ concentration and open in response to rise in intracellular calcium (not coupled to voltage gated Ca2+ channels as are in skeletal muscle) - release large amount of Ca2+ into the myoplasm
   The free Ca2+ concentration increases to 1 uM
3. Sufficient force is produced to maintain cardiac output
4. Removal of Ca2+ via Na/Ca exchanger and pumped back into the SR via SR Ca ATPase (SRCA)

Question 4

Calcium induced calcium release

Answer 4

Process where small amount f calcium entering the cell produces a much larger release of calcium through the SR
-i.e. type of Ca2+ release in myocardial cells

Question 5

Effect of stimulating B1 adrenergic receptors

Answer 5

• increase in heart rate (positive chronotropic effect)
• increase in force of contraction (positive inotropic effect)
• increase in rate of relaxation (positive lusitropic effect)

Question 6

MOA of stimulation B1 adrenergic receptors

Answer 6

All changes produced through action of protein kinase A on key regulatory proteins that regulate the intracellular Ca2+ concentration

Question 7

MOA positive chronotropic effect

Answer 7

• phosphorylation of voltage-gated Ca2+ channels increases it open probability
• increases the amount of Ca2+ entering cell
• increased frequency of contraction = increase heart rate

Question 8

MOA positive inotropic effect

Answer 8

• phosphorylation of phospholamban
• phospholamban moves away from SR/ER CaATPase -release inhibition = SERCA increase velocity
• more Ca2+ pumped into lumen of SR = more available to be released through RyR
• increased force of contraction and rate of frce development

Question 9

MOA positive lusinotropic effect

Answer 9

• phosphorylation troponin
• decreases troponins affinity for calcium (even in high Ca2+ conc.)
• in combo with increased rate of Ca2+ removal by SERCA increases the rate at which cell relaxes

Question 10

Sources of ATP for the heart

Answer 10

#1 = fatty acid (70%)
#2 = glucose oxidation (20%)
#3 lactate (10%)
-creatine phosphate does not create new ATP but stores previously made ATP
-glycolysis cannot support the metabolic demands of the myocardium (must have fa and O2)