Cardiac Pacemaker Cells

• Where are electrical impulses generated from?

  Cardiac pacemaker cells
• Where do electrical impulses spread across?

  The myocardium
• What do electrical impulses spreading across the myocardium produce?

  Systole of the heart- coordinated contraction
• How is an AP generated?

  A change in PD between the inside and outside of the cells
• Where are most pacemaker cells?

  SAN: Upper wall of the right atrium
• What do pacemaker cells have?

  Natural automaticity- they can generate their own impulses
• What are the AVN and Purkunje fibres and what does this mean?

  Latent pacemaker cells- they are capable of pacemaker activity.
• Why does SAN dominate over AVN and other pacemaker cells?

  The SAN has the fastest pacing rate so other cells are overridden
• Draw a graph to show the action potential of an SAN?

  
• What are the phases of a SAN AP?

  Phase 4: pacemaker potential

  Phase 0: Depolarisation

  Phase 3: Repolarisation
• What happens in phase 4: the pacemaker potential of the SAN?

  - Occurs at the end of 1 AP before another

  - The slow depolarisation of the pacemaker cells towards the membrane potential threshold. This is called the "funny current" or If current

  - Once the membrane potential is -50mV or lower HCN channels are activated which allow Na+ to enter the cell

  - Once the membrane is depolarised to meet the threshold, an AP can occur
• What happens in phase 0: depolarisation of the SAN?

  - Once the HCN channels have brought the membrane potential to -40mV, voltage-gated calcium channels open

  - Influx of calcium which produces a faster rate of depolarisation to reach a positive membrane potential

  - HCN channels start to inactivate

  - At peak of AP Ca2+ channels inactivate and K+ channels activate
• What happens in phase 3: repolarisation of the SAN?

  - Once the ca2+ channels inactivate, K+ channels open

  - K+ efflux out of cells

  - Results in membrane depolarisation
• How is the SAN AP different to the ventricular AP?


  The SAN AP doesn't have sustained opening of the Ca2+ channels, so there is no plateau stage
• What happens following repolarisation?

  The membrane potential must reach negative values

  This reactivates HCN channels

  Another AP is generated
• What can alter the slope of the pacemaker potential?

  ANS: Parasympathetic and sympathetic branches
• What effect does altering the pacemaker potential have?

  Alters heart rate
• What mediates the parasympathetic branch?

  Mediated by acetylcholine acting on M2 muscarinic receptors on SAN
• What effect does the parasympathetic branch have?

  This increases the interval between the pacemaker potential, decreasing the heart rate
• What mediates the sympathetic branch?

  Mediated by noradrenaline acting on B1 adrenorecptors
• What effect does the sympathetic branch have?

  This decreases the interval between the impulses by making the pacemaker potential steeper, hence increasing heart rate
• If all autonomic input to the heart is blocked, what is the intrinsic heart rate?

  100bpm
• What is the normal resting heart rate and why?

  60bmp as the parasympathetic system dominates at rest
• What brings about initial increases in heart rate?

  A reduction in parasympathetic outflow
• What is an arrhythmia?

  A heartrate with an irregular beat/rhythm
• What can cause arrhythmias? (3)


  A disturbance to the natural pacemaker activity of the heart

  - Ectopic pacemaker activity

  - After-depolarisations

  - Re-entry loops
• What happens in ectopic pacemaker activity?


  When another area of the myocardium becomes spontaneously active and its depolarisations dominate over the SAN
• When can latent pacemaker regions become active?


  In ischaemic damage
• What are after-depolarisation arrhythmias?


  When abnormal depolarisations follow the AP

  Caused by high intracellular Ca2+
• What is a re-entry loop?


  When the normal spread of excitation across the heart is disrupted due to a damaged area
• What happens when the conduction damage is incomplete?


  The impulse can spread the wrong way through the damaged area and create a circle of excitiation
• How can re-entry loops lead to atrial fibrillation?


  Multiple small re-entry loops in the atria
• Why are arrhythmias dangerous?


  They allow blood to collect in the heart chamber and form clots, leading to increased stroke and MI risk
• What can an arrhythmia in the ventricles lead to?


  Cardiac arrest
• What is the treatment for arrhythmias?

  DC cardio version- shock the heart into a regular rhythm

  Rhythm controlling drugs like amiodarone