L6.2 Cardiac muscle cell: Electro-mechanical coupling Flashcards Preview

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Flashcards in L6.2 Cardiac muscle cell: Electro-mechanical coupling Deck (15):
1

Overview of Ca signaling in sarcomeres

2

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

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

3

[Ca] transmembrane potentials

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

4

Ionic transporters in the sarcolemma

  • 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)

5

Ca ATPase

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

6

Na/Ca exchanger

  • 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

7

Is internal or external cycling of Ca more porminent

Internal cycling is 4x > than external

8

% of Ca influx via:

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

9

% of Ca efflux via:

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

10

Reversible Na/Ca exchanger

  • 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

11

Na/K ATPase

 

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

 

12

H prod (by metabolic actions inside cell)

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

13

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

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

14

Na/K ATPase inhibitor

  • 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

15

CPVT disease

  • 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)