l12

• Sinoatrial node pacemaker potentials

  • Upstroke of the slow pacemaker action potential
  • Triggered at the threshold potential (~ -55 mV)
  • Increase in movement of Ca2+ into cell
  • Increase in K+ efflux
  • Membrane hyperpolarises
• Sinoatrial node pacemaker potentials - Phase 4

  • Prepotential
  • Permits automaticity
  • Activated by hyperpolarisation (Phase 3)
  • HCN mediates a 'funny current' (If)
  • Simultaneous K+ efflux and Na+ influx
  • Na influx dominates causing slow depolarisation of membrane
  • Reaches threshold
  • Upstroke inactivates HCN
• Pacemaker cell membranes


  Contain HCN-gated channels (Hyperpolarisation-activated, cyclic nucleotide-dependent nonspecific channel)
• Ventricular myocyte action potentials


  1. 0 Na+ channels open

  2. 1 Na+ channels close; fast K+ channels open

  3. 2 Ca2+ channels open; fast K+ channels close

  4. 3 Ca2+ channels close; slow K+ channels open

  5. 4 Resting potential
• Sympathetic nerves activated


  • Causes release of noradrenaline
  • Binds to b1 adrenoceptors on the cardiac pacemaker and myocyte cell membranes
  • Increases opening of HCN channels in pacemaker cells
  • Increase Na+ influx; If
  • Opens Ca2+ channels
  • Increased Ca2+ influx
  • Increase in slope of prepotential (Phase 4)
  • Heart rate increases
• Parasympathetic nerves activated


  • Causes release of acetylcholine
  • Binds to muscarinic cholinergic receptors
  • Decreases opening of HCN channels
  • Decreased Na influx
  • Slows opening of Ca2+ channels
  • Decreased Ca2+ influx
  • Opens additional K+ channels (ligand gated)
  • Increased K+ efflux
  • Hyperpolarises membrane and reduces slope of prepotential
  • Heart rate decreases
• Vagal tone to the heart
• Early afterdepolarizations (EADs)


  • Occur when normal heart rate low
  • Suppressed by high heart rate
  • Occur when AP prolonged
  • Some Ca channels inactivate during shoulder
  • Reactivate to give EAD
  • Ca L channels: end phase 2
  • Ca T channels: mid phase 3
  • Need different drugs to Rx
• Delayed afterdepolarizations (DADs)


  • Seen at increased heart rates
  • Associated with elevated [Ca2+]
  • ICa2+ activation of Na/K channels
  • Iti (depolarising)
  • NaCa exchange 3:1 – electrogenic
  • Toxic doses of cardiac glycosides
• Vaughan Williams Classification


  Classes of drugs to treat abnormal heart rhythms
• Vaughan Williams Classification - Slow heart rhythms or bradycardias


  • Need to increase heart rate
  • Atropine - switch of vagus nerve
  • Isoproterenol (isoprenaline) - activate beta receptors
  • Pacing
• Isoproterenol


  Activate beta receptors
• Vaughan Williams Classification - Drugs to treat abnormal fast heart rhythms - tachycardia


  • Class I - Na channel blockers
  • Class II - Beta blockers
  • Class III - K channel blockers
  • Class IV - Ca channel blockers
• Class I - Na channel blockers


  • Lidocaine/lignocaine
• Class II - Beta blockers


  • atenolol, metoprolol, sotalol
• Class III - K channel blockers


  • amiodarone
• Class IV - Ca channel blockers


  • verapamil