Cardiac Action Potential

The Pacemaker Potential

The pacemaker potential is the automated, rhythmic depolarisation of the sinoatrial node cells that provide the heart with its intrinsic rhythm.

When describing cardiac action potentials, there are 5 phases, numered 0 to 4

  • The pacemaker potential only has phases 0, 3 and 4
    • Phase 0
      • Depolarisation is triggered at -40mV
      • Slow L type calcium channels cause slow calcium ingress into the cell
    • Phase 3
      • Repolarisation
      • Calcium channels close
      • Potassium channels open
    • Phase 4
      • Transient ‘overshoot’ hyperpolarisation reaching maximum diastolic potential of -65mV
      • Potassium channels close
      • Gradual depolarisation until the threshold potential is met, due to:
        • Sodium ion leak
        • T Type calcium channels allowing calcium in
        • Sodium-calcium pump

Sympathetic and parasympathetic stimultion cause the gradient of phase 4 to be steeper and shallower respectively

The Cardiac Action Potential

The trace of the action potential seen in cardiac myocytes is different, as rather than being rhythm generators, they use the action potential to generate a sustained contraction during systole. As mentioned above, there are five phases to the cardiac action potential, labelled 0 to 4

  • Phase 0
    • Rapid depolarisation
    • Fast sodium channels
  • Phase 1
    • Repolarisation (short)
    • Sodium channels close
    • Potassium channels open
    • Does not repolarise beyond zero mV
    • Part of absolute refractory period
  • Phase 2
    • Plateau phase
    • L type calcium channels allow calcium in to slow repolarisation
    • Part of absolute refractory period, hence heart muscle cannot demonstrate tetany
  • Phase 3
    • Repolarisation
    • L type calcium channels close
    • Potassium channels continue to allow potassium out
    • Part of relative refractory period
  • Phase 4
    • Sodium potassium ATPase returns membrane potential to baseline
    • Part of relative refractory period

Classifying antiarrhythmics

  • The ‘old-fashioned’ way to classify antiarrhythmic agents is the Vaughan-Williams classification based on their target ion channel as described in this video

However this isn’t much use as it doesn’t cover the relatively commonly used drugs such as digoxin and adenosine (these have been retrospectively ‘added’ to the VW classification in the video above).

Also drugs such as amiodarone and sotalol don’t really fit into a single group and have actions at multiple receptor sites.

  • They can also be categorised by their indication
  • SVT
    • Adenosine
    • Beta blockers
    • Verapamil
    • Digoxin
  • VT
    • Lidocaine
  • SVT and VT
    • Amiodarone
    • Procainamide
    • Flecainide
  • Phenytoin is used for digoxin toxicity

Which aspects of the cardiac action potential do each class of antiarrhythmic agent act on?

  • Class 1 drugs are membrane stabilisers and they inhibit the rapid influx of sodium ions responsible for phase 0 of the the action potential
    • They also reduce the rate of phase 4 depolarisation in the pacemaker cells
      • IA prolong the refractory period, acting in the atria, ventricles and accessory pathways
      • IB shorten the refractory period, only acting in the ventricles
      • IC have no effect on the refractory period, acting in the atria, ventricles and accessory pathways
  • Class 2 drugs are beta blockers, inhibiting sympathetic tone on the heart. They have the following three effects:
    • Reduction of the slope of phase 4 depolarisation (pacemaker cells)
    • Reduction of the maximum rate of depolarisation (phase 0)
    • Prolonging the duration of the action potential
  • Class 3 drugs prolong the duration of the action potential and refractory period by inhibiting potassium channels
  • Class 4 drugs modify the plateau phase in non-pacemaker cells and inhibit depolarisation in phase 0 of pacemaker cells by inhibiting calcium channels

Why do children frequently develop bradycardia in response to an insult?

  • Their parasympathetic systems are more developed than their sympathetic system, so anything that causes high autonomic stimulation will produce dominant parasympathetic responses, such as bradycardia

What considerations do you need to make regarding heart rate in heart transplant patient?

  • There is loss of innervation to the heart, meaning any drugs that alter heart rate via parasympathetic or sympathetic stimulation will not work
    • Atropine and glycopyrrolate will not increase heart rate
    • Ephedrine will only work via its direct action (indirect agents have no effect)
    • Adrenaline and isoprenaline will increase heart rate

Why do tachyarrhythmias occur?

  • Increased automaticity of atrial or ventricular myocytes resulting in premature depolarisation before the sinoatrial note
  • Can be triggered by anything that encourages the membrane potential to reach the threshold for depolarisation too quickly, such as ionic imbalance, particularly hypokalaemia, and ischaemia
  • Re-entry tachyarrhythmias can occur if there is an ectopic focus and a conducting pathway that allows a circuit of repolarisation and depolarisation to occur

Why might a patient become bradycardic?

  • This could be a physiological response or a pathalogical conduction issue
  • Physiological response
    • Vagal stimulation
      • Surgical
        • Pneumoperitoneum
        • Cervical dilatation
        • Pressure on the eye
      • Anaesthetic
        • Laryngoscopy, particularly using a Miller blade in children
          • The Miller blade lifts the underside of the epiglottis, which is innervated by the vagus, rather than the valleculae which are innervated by the glossopharyngeal nerve
        • Medication
          • Opioids
          • Neostigmine
  • Conduction pathology
    • Failure of AV node to conduct atrial impulse to conducting system
      • Type II or complete heart block
        • MI
        • Ischaemia

Antiarrhythmics summary

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