Molecular Mechanisms of Arrhythmias Flashcards Preview

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Flashcards in Molecular Mechanisms of Arrhythmias Deck (14)

Define a Long-QT Syndrome

Delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsades de pointes

  • These episodes may lead to palpitations, fainting, and sudden death due to ventricular fibrillation


Define Torsades de Pointes

  • Form of irregular heartbeat that originates from the ventricles


What gene defects are associated with a long-QT syndrome?

Autosomal Dominant Form

  • slow cardiac K+ channel IKs (LQT1)
  • Rapid cardiac K+ channel IKr (LQT2)
  • Cardiac Na+ channel INa (LQT3)

Auto Recessive Form

  • Homozygous IKs (LQT1) suffer in addition from congenital deafness - hetero's are asymptomatic



Outline the two molecular basis for a long-QT syndrome?

*Note: depending on which one it is, treatment is different

  1. Mutations reduce number of K+ channels expressed in the myocyte plasma membrane (loss of function mutation)
    • Reduces size of K+ current that helps terminate plateau phase of the fast response
  2. Mutations prevent Na+ channels from inactivating completely (gain of function mutations)

    • Thereby prolonging phase 2 of the fast response


What is the name of Class I antiarrhythmic drugs?

Na+ channel blockers


What are the 3 ion channels targeted by class I antiarrythmic drugs and what phases of the slow & fast response do they target?

  1. Ia: Slow the upstroke of the fast response (phase 0), prolong refractory period (phase 4) because depolarization (phase 2) is prolonged.
  2. Ib: Slow upstroke (phase 0) mildly, shorten depolarization (phase 2) and prolong refractory period (phase 4).
  3. Ic: Pronounced slowing of the upstroke of the fast response (phase 0), mildly prolong depolarization (phase 2).


What is the name of Class II antiarythmic drugs?

Beta-adrenergic receptor blockers


What ion channels and phases of the slow and fast response does class II antiarrythmic drugs target?

  • LTCC, and K+ current
  • reduces the rate of diastolic phase 4 depolarization in pacing cells, reduces the upstroke rate and slows repolarization.


Class III Antiarrythmic Drugs

  1. Name
  2. What phases do they target?

  1. K+ channel blockers
    • Prolongation of fast response phase 2
    • Prominent prolongation of refractory period.


Class IV Antiarrythmic Drugs

  1. Name
  2. Phases of the slow & fast response targeted

  1. Ca2+ channel blockers


    • Slow the Ca2+ -dependent upstroke in slow response tissue (slow rise of action potential)

    • Prolong the refractory period (prolonged repolarization)


What phases are effected in an early afterdeporlarization (EAD)?

  • Phases 2 & 3
    • caused by an increase in the frequency of abortive action potentials before normal repolarization is completed
    • Phase 2 due to augmented opening of calcium channels
    • Phase 3 interruptions due to the opening of sodium channels


What phase is affected in a delayed afterdpolarization (DAD)?

Phase 4

  • After repolarization is completed but before another action potential would normally occur
  • Due to elevated cytosolic calcium concentrations
    • Classically seen with Dogoxin toxcitiy


What is a Re-entry arrythmia?

  • Electric signal not completing the normal circuit, but rather an alternative circuit looping back upon itself
    • Causes Paroxysmal tachycardia occurring in the ventricle


What two conditions are required for a Re-entry arrythmia?

Reentry occurs when there is a unidirectional block and slowed conduction through the reentry pathway

  • After the slow reentry the previously depolarized tissue has recovered and reentry into it will occur.