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

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

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


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

Phase 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 


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


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


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


Does the addition of extracellular calcium affect contraction?

Yes - increases the force of contraction


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


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 


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


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 


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


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

Binds to Troponin C


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

Reuptake by the SR Ca-ATPase 

80% of rate of decline 


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


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


What effect do catecholamines have on SA nodal cells?

Heart rate is increased 

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


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 


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 


What are the characteristics of myosin?

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


What are the characteristics of actin?

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


What is the function of tropomyosin?

Modulates actin-myosin interaction


What is the function of Troponin C in sarcomere contraction?

Calcium binding 


What is the function of Troponin I in sarcomere contraction?

Inhibits actin-myosin interactions


What is the function of Troponin T in sarcomere contraction?

Binds tropoin complex to the thin filament 


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 


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


Describe the troponin complex

Troponin T binds to tropomyosin

Troponin I and Troponin C bind to Troponin T


What is the structure of Troponin C?


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 


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


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


What causes a state of rigor in muscles?


Myosin and actin need ATP to unbind


Does the binding of actin to myosin require ATP?


Binding of actin to myosin is a spontaneous event