EXAM #1: MECHANISMS OF DYSRHYTHMIAS Flashcards
What phases of the cardiac myocyte action potential correspond to the absolute refractive period?
0, 1, and 2
What phase of the cardiac myocyte action potential corresponds to the relative refractive period?
3
What are the two important parts of the Na+ channel related to the refractory periods?
1) Inner pore
2) Inactivation gate
What is the conformational state of the Na+ channel during the resting membrane potential?
- Inner pore is closed
- Inactivation gate is open
What happens to the confirmation of the Na+ channel during depolarization?
Depolarization= conformational change that OPENS the inner pore
After depolarization, what causes the inactivation gate to plug the Na+ channel?
Time after depolarization
What is the outcome of the Na+ channel being plugged with the inactivation gate?
Absolute refractory period
What causes the inactivation gate to unplug the Na+ channel?
More time
How does the relative refractory period relate to the inactivation gate?
- The inactivation gate is in the process of moving out of the way
- STRONG impulse CAN cause an action potential
What effect does a Na+ channel blocker have on the cardiac action potential?
Prolongs the absolute refractory period
What is excitation contraction coupling?
Coupling of electrical stimulus with mechanical contraction
How does excitation-contraction coupling in cardiac muscle compare to skeletal muscle?
Time delay= ~150 m/sec, which is MUCH LONGER than skeletal muscle
Outline excitation-contraction coupling in cardiac muscle cells to cause contraction.
1) Depolarization opens voltage-gated Ca++ channels
2) Ca++ influx
3) Ca++ binds RyR on SR
4) Ca++ induced Ca++ release from the SR
5) Ca++ binds troponin
Contractile shortening of the sarcomere occurs
Outline relaxation in cardiac muscle cells.
1) Ca++ dissociates from Troponin
2) Ca++ is taken up into SR via SERCA (SR Ca++ pump)
3) Ca++ binds proteins in SR e.g. calsequestrin
4) Ca++ is pumped OUT via
- Na+/Ca++ exchanger
- Ca++ pump
What is the difference between Ca++ handing in skeletal and cardiac muscle cells?
- In SKELETAL m. Ca++ channel is in CONTACT with RyR
- In CARDIAC m. Ca++ influxes into the cell, THEN binds with RyR on SR for Ca++ release
Generally, what is the stimulus for contraction of a cardiac myocyte? Relaxation?
Intracellular Ca++= contraction
Lack of intracellular Ca++= relaxation
What is one element of the pathology of HF that underlies contractile impairment?
Limited Ca++ influx= less Ca++ induced Ca++ release
–>Less cardiac contractility
Generally, what is an active arrhythmia?
Change in automaticity
- E.g. nodal cells w/ phase 4 depolariztion
What happens in the SA node for sinus brady and tachycardia?
Tachycardia= increased slope of diastolic phase 4 depolarization
Bradycardia= decreased slope of diastolic phase 4 depolarization
How does sympathetic stimulation increase HR?
1) Activating HCN (funny current)
2) Increasing Ca++ influx
How does parasympathetic stimulation decrease HR?
1) ACh
2) ACh causes INCREASED K+ current
–>Decreased phase 4 depolarization
What are the types of triggered arrhythmogenesis?
Delayed After Depolarization
Early After Depolarization
What is a delayed after depolarization (DAD)? EAD?
DAD= arrhythmia generated during phase 4 EAD= arrhythmia generated during phase 2 or 3
What causes DADs?
Increased Ca++, which can be either:
- Cytosolic
- SR
What causes EADs?
- Altered ion flux during plateau phase of AP
- Characterized by extended APD
List mechanisms that will prolong the APD.
1) Reduced K+ current opposing Ca++
2) Increased Ca++ opposing K+
3) Increased Na+/Ca++ exchange activity
4) Increased late Na+ current
Why can EADs be exacerbated by low HR?
APD is already long in low HR
List the mechanisms that will lead to DADs.
1) Mutation in Ca++ binding proteins
- Calsequestrin
- SERCA
2) High HR
Why are DADs exacerbated by high heart rates?
- Short APD
- Less time for Ca++ sequestration/ cycling
What is a reentrant circuit?
Impulse travels via an accessory pathway in the conduction system
List the examples of re-entrant circuits.
1) WPW
2) AVNRT
3) A-flutter
4) PSVT
How is anatomical re-entry treated?
Ablation
What is a functional re-entry circuit?
- Absence of a defined anatomical pathway
- Spatial or electrical differences between cells generate difference in conduction
E.g. from ischemia or infarction
What are examples of functional re-entry?
1) Monomorphic VT
2) Polymorphic VT/VF
What does circus movement re-entry rely on?
Unidirectional block of conduction
