Electrical Activity

Question 1

Generation of AP in Ventricle Cells (4 parts)

Answer 1

• Resting membrane potential = -90 mV (mainly based on K+ efflux - IK1 current); STABLE
  
  • Kir2.1 channel protein
• Upstroke - Na+ influx once threshold of -65 mV reached
  
  • Threshold —> voltage-gated m gate opens —> once near +40 mV inactivation h gate shuts
  • All-or-nothing; positive feedback b/c as Na+ enters cell the cell becomes more positive which opens more Na+ channels
• Plateau - K+ efflux, Ca++ influx, Na+ current and Na/Ca exchangers all contribute
  
  • L type Ca++ channels
  • IK1 current dec in plateau b/c higher potential BUT there are 2 other TIME DELAYED K efflux currents at this time (IKr and IKs - rapid and slow repolarizing currents)
• Refractory Period - unable to propagate new AP
  
  • Full Recovery Time = effective refractory period (no AP) + relative refractory period (higher threshold for AP)

Question 2

How are L Type Ca++ Channels inactivated?

Answer 2

1- Ca++ dependent (high Ca++ in cell turns off L type channels faster)

2- Voltage dependent

Question 3

Generation of AP in SA Node Cells

Answer 3

• Resting membrane potential is NOT stable; slowly depolarizes until reaches threshold for another AP (-45 mV); this slow depolarization is called pacemaker potential
• 2 Possible Mechanisms
  • I. Funny channel - cAMP and hyper-polarization turns on HCN channel protein; positive influx of Ca++ and Na+
  • II. Ca++ Clock -
    
    • Spontaneous release of Ca++ from SR —> Ca/Na exchange to remove Ca from cell —> net depolarization (b/c 3 Na+ in for 1 Ca++ out) —> depolarization act L type channels —> AP then SR reloaded w/ Ca++ from cytosol and it starts again

Question 4

2 Ways Cardiac Musc Cells are Diff Than Skeletal Musc Cells

Answer 4

• Cardiac muscle cannot contract w/ just Ca++ from SR (needs extracellular Ca++ influx too)
• Plateau instead of rapid repolarization by K+ efflux

Question 5

3 Steps of Excitation-Contraction Coupling in Ventricles

Answer 5

• 1- Na+ upstroke depolarizes cell membrane —> depolarizes T tubules
• 2- Depolarization opens voltage-gated L type Ca++
  channels —> Ca++ influx
• 3- Inc Ca++ in cell causes inc Ca++ release from SR via RYR2 (“calcium induced calcium release”)

Question 6

How is Ca++ removed from cardiac muscle cell?

Answer 6

• Pumped back into SR via SERCA2 (requires ATP)
• Na+/Ca++ exchanger (3 Na+ in for 1 Ca++ out - overall depolarizes cell); extra Na+ then removed by Na-K pump
• Ca++ transporters on cell membrane surface (requires ATP)

Question 7

Staircase/Bodwitch Effect

Answer 7

• Changing HR changes force of contraction in about 12 incremental steps (12 beats)
  
  • Inc HR = Inc Force (positive inotropic effect)
• How?
  
  • Inc HR means AP duration is shorter; less time for Ca++ efflux so overall Ca++ accumulates in cell

Question 8

How does sympathetic NS affect electrical activity?

Answer 8

• Affects ventricles the most
• Activates channels —> reaches AP threshold faster —> inc firing frequency/HR
  • Force of contraction inc but duration dec
  • Adrenaline binds beta1 adrenergic receptor —> activates adenylyl cyclase —> inc cAMP—> activate protein kinases …
    
    • Funny channel activation
    • Phosphorylate phospholamban so no longer blocks SERCA2
    • Phosphorylate RyR2 for inc Ca++ release
    • Phosphorylate/activate L type channels
    • Inc K+ efflux for more rapid repolarization

Question 9

How does parasympathetic NS affect electrical activity?

Answer 9

• Affects SA node cells > AV node cells > ventricle cells
• Vagus —> Ach
  • Binds Gi (inhibitory G protein) —> inc cGMP which inhibits adenylyl cyclase from making cAMP (ONLY COUNTERS EFFECTS OF ADRENALINE)
  • Creates K+ efflux that hyper polarizes cells so less steep pacemaker potential; takes longer to reach AP threshold

Question 10

What happens in channelopathies in general?

Answer 10

QT prolongation —> Torsade de Pointes

* How? 
    * Prolonged AP —> more Ca++ influx via L type channels
    * Compensate w/ Na-Ca exchanger which has net depolarization effect —> makes AP duration even longer
    * SR becomes overloaded w/ Ca++ —> spontaneous release from SR —> triggers EADs (early after-depolarizations); oscillations in Ca++ conc in cell —> EADs