Cardiac EC Coupling (B 2: W 2) Flashcards Preview

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Flashcards in Cardiac EC Coupling (B 2: W 2) Deck (33):
1

What is the relationship between the ventricular action potential and the contraction?

There is one action potential for each contraction

There is a delay in eliciting a ctonraction

2

At which phase in the ventricular action potential is the peak contraction

Phase 3

3

What is the T tubule of a sarcomere and how does it function?

T tubule is an invagination of the plasma membrane into cell (skeletal and cardiac muscle)

Allows for rapid and homogenous spread of excitation to the center core of cell

  • Electric signal travels across plasma membrane
    • Contiguous membrane allows action potential to go inside cell
  • Directly connected to the sarcoplasmic reticulum - reserve of calcium
  • SR releases calcium to myofibrils to activate contraction - triggered by AP 

4

How does cardiac muscle react to the removal of extracellular calcium? Skeletal muscle?

Cardiac muscle does not contract in the absence of extracellular calcium

Ca-dependent contraction 

Skeletal muscle contractions increase in the absence of calcium

5

Why are T tubules in cardiac cells 5 times larger than in skeletal muscle? 

Because cardiac cells require calcium to contract

Thinner T tubules would yield extracellular calcium depletion

6

How does extracellular calcium trigger increase in intracellular calcium to cause contraction?

  • Extracellular calcium ions travel through voltage gated channels
  • Bind to RyR (ryanodine receptor)
    • Release of Ca from sarcoplasmic reticulum
  • Calcium induced calcium release

7

Does the addition of extracellular calcium affect contraction?

Yes - increases the force of contraction

8

What are the mechanisms for reducing calcium levels in a cell to cause relaxation?

  • Reuptake of calcium by Ca-ATPase in sarcoplasmic reticulum
  • Na-Ca exchange pump (NCX)
    • No ATP
    • Uses energy from Na gradient to pump Ca out
    • 3 Na: 1 Ca
  • Plasma membrane Ca pump: uses ATP

9

What are the roles of calcium current in cardiac excitation-contraction coupling?

  • Responsible for maintaining the long plateau of the action potential
  • Triggers the release of Ca ions from the sarcoplasmic reticulum
    • Amplification of the plasma membrane signal
  • Refills the sarcoplasmic reticulum Ca stores to be used in subsequent beats 

10

How does the injection of a depolarizing current during a ventricular action potential affect contraction? Hyperpolarizing current? 

AP shape is important for EC coupling 

  • Depolarization of one AP increases force of contraction on the next beat
    • Opened more Calcium channels, accummulated in SR, released on following beat
  • Hyperpolarization of one AP decreases force of contraction in second beat

11

What happens in the case of premature systole?

  • The premature systole is depressed - channels have not had time to recover from activation
  • Second beat is stronger - extra calcium causes a transient increase 

12

What happens when there is an increase in stimulation (increase in pacemaker activity)?

  • Progressive increase of force over time
    • More calcium is entering voltage-gated Ca channels
    • More is being reuptaken into SR

13

How does the calcium, entering the cell and being released by SR, activate muscular contraction?

Binds to Troponin C

14

Which mechanism for calcium relaxation accounts for the highest decline in calcium concentration?

Reuptake by the SR Ca-ATPase 

80% of rate of decline 

15

Describe the mechanism for catecholamine activation of ß-adrenergic receptors in cardiac muscles. 

  • Epi/NE binds to ß receptor
    • Coupled to a Gs protein
  • Alpha G activates adenylyl cyclase
    • Produces cAMP
  • cAMP activates PKA
  • PKA phosphorylates several targets

16

What are the two mechanisms of increasing contraction in the heart? 

  1. PKA phosphorylates voltage-gated Ca channel
    1. Activity enhanced
    2. More Ca enters cell, causes more to be released from SR
  2. PKA phosphorylates PLB (phospholambin) to enhance Ca-ATPase reuptake activity into SR
    1. More Ca delivered in following beats
  3. Questionable third method: enhances coupling of Ca to RyR

17

What effect do catecholamines have on SA nodal cells?

Heart rate is increased 

Same pathway as in ventricular cells - increases activity of Ifunny current 

18

What are the two mechanisms of relaxation when catecholamines stimulate ß adrenergic receptors of the heart?

  • PKA phosphorylates PLB (phospholambin) 
    • Increases activity of Ca-ATPase
    • Faster reuptake of Ca into SR - relaxation
  • PKA phosphorylates Troponin I
    • Desensitizes troponin C to calcium
    • Accelerates relaxation 

19

Are cardiac contractions large or small?

Very small

Contraction is constrained within about 2 micron distance

Goes from 2 to 1.5 microns

20-25% contraction 

20

What are the characteristics of myosin?

  • High molecular weight
  • 2 heavy chains, 4 light chains
  • Polar heads spiral around 
  • Site of ATP hydrolysis 

21

What are the characteristics of actin?

  • The main thin filament 
  • Myosin heads bind to actin
  • Activates myosin ATPase

22

What is the function of tropomyosin?

Modulates actin-myosin interaction

23

What is the function of Troponin C in sarcomere contraction?

Calcium binding 

24

What is the function of Troponin I in sarcomere contraction?

Inhibits actin-myosin interactions

25

What is the function of Troponin T in sarcomere contraction?

Binds tropoin complex to the thin filament 

26

What role do the heavy chains and light chains have in myosin?

  • Light chains play a role in force of contraction in cardiac muscles
  • Heavy chains control contraction

There are many isoforms of myosin in the heart with different ATPase activities 

27

How does tropomyosin inhibit actin-myosin interaction?

Tropomyosin lies on actin and prevents myosin from binding

When it moves, it allows actin and myosin to bind

28

Describe the troponin complex

Troponin T binds to tropomyosin

Troponin I and Troponin C bind to Troponin T

29

What is the structure of Troponin C?

"Dumbell"

4 potential binding sites for Ca and magnesium 

I and II are Ca acceptor sites specifically

III and IV can bind Ca, but bing Mg if concentration is high 

30

How does Troponin I function in the absence of calcium?

  • Troponin I is not activated 
    • Pulls whole complex away from group - prevents interaction of actin with myosin 
  • In the presence of calcium, Ca binds Troponin C, and switches
    • Actin-myosin interaction

31

Describe the molecular cycle of contraction

  • ATP binds to polar heads of myosin
  • Hydrolysis by myosin ATPase - now it is relaxed and energized
    • Allows for binding of myosin head to actin filaments
  • Once it binds, triggers change in angle of polar head
    • Pulls the actin
    • Motion and force being produced
  • Now ATP needs to bind so molecule can come back to relaxed state
    • ATP is necessary for unbinding and for hinge to be at normal angle

32

What causes a state of rigor in muscles?

Low ATP

Myosin and actin need ATP to unbind

33

Does the binding of actin to myosin require ATP?

No 

Binding of actin to myosin is a spontaneous event