L6.2 Cardiac muscle cell: Electro-mechanical coupling

Question 1

Overview of Ca signaling in sarcomeres

Answer 1

Question 2

What triggers the release of Ca from SR in cardiac cells?

Answer 2

• Only need a few Ca ions into the fuzzy space to cause the release of Ca from SR

Question 3

[Ca] transmembrane potentials

Answer 3

• Outside = 2mM
• Cytosol = 100nM
• SR = 1mM
  
  • Difference was 10000x → potential store for contraction initiation

Question 4

Ionic transporters in the sarcolemma

Answer 4

• Pumps - uses ATP (1 way - against gradient)
• Exchanger - No ATP needed (could be reversible)
• Takes time for Ca to be reuptaken/removed from cell (Slow)

Question 5

Ca ATPase

Answer 5

• SERCA
• Reuptake Ca into SR requires energy
• Causes relaxtion (diastole)

Question 6

Na/Ca exchanger

Answer 6

• Exchange Ca out (remaining Ca not reuptaken)
• 1 Ca out, 3 Na in
  
  • Na usually low inside
• Counter productive to achieve RMP
  
  • Destabilises RMP → risk of arrhythmia
• But useful for relaxation

Question 7

Is internal or external cycling of Ca more porminent

Answer 7

Internal cycling is 4x > than external

Question 8

% of Ca influx via:

Answer 8

• Ca channels = 20% (from outside)
• SR = 80% (from inside)

Question 9

% of Ca efflux via:

Answer 9

• Na-Ca exchanger = 19%
• Sarcolemmal Ca pump = 1%
• SERCA = 80%

Question 10

Reversible Na/Ca exchanger

Answer 10

• 1 Ca in, 3 Na out
• Mostly in fuzzy space
• Entry early in AP (During depol when Na influx)
• Depends on conc of ions intra/extracellularly

Question 11

Na/K ATPase

Answer 11

• Restoring Na levels
  
  • 3 Na out, 2 K in
• stabilises RMP

Question 12

H prod (by metabolic actions inside cell)

Answer 12

• Corrected by Na/H
• 1:1 Na/H exchanged → electroneutral

Question 13

Na/Ca & Na/H poses what problems and how is it solved?

Answer 13

• Causes overload of Na
• Solved:
  
  • Na/K ATPase → Restores Na overload
  • K out via K channels (repol)

Question 14

Na/K ATPase inhibitor

Answer 14

• Has glycosides → which inhibits Na/K ATPase (good for heart failures)
  
  • Increases background [Na] in heart cells
  • Limits Na/Ca exchanger to remove Ca
  • Increase SR Ca loading → increase contraction
• BUT → SR may be overload with Ca & be oversensitised → increase Ca release
  
  • Depol cells → AP spread through heart → ectopic arrhythmia
    
    • Getting more positive near threshold → spreads via Ca/Na exchanger
  • Eat bananas → restore K → cure

Question 15

CPVT disease

Answer 15

• Catecholaminergic polymorphic ventricular tachycardia
• Leaky SR release channel
  
  • RyR 2 protein mutations (autosomal dominant)
    
    • RyR hypersensitive to Ca → arrhythmia
• Vulnerable during NA/A surge (exercise)
• Detected only post mortem
• b-blokcer treatment needed (life-long)