Cardiac electrophysiology and Cardiac Arrhythmias Flashcards
Draw and describe the phases of cardiac action potential. Which channels areopen and which currents are responisble for each phase?
Phase 0: depolarization; Na+ current (open fast Na+ channels)
Phase 1: partial repolarization; Ito (outward K+ current that drives Vm to be more negative)
Phase 2: plateau (sustained depolarization); Ca2+ current
Phase 3: repolarization; Ik (delayed action)
Phase 4: rest
Which cells undergo the fast response? What about the slow response? Why don’t the slow response cells have a Phase 1? Explain the difference between slow and fast response. What are ERP and RRP?
Non-pace maker cells undergo the fast response b/c they have fast Na+ channels
Pacemaker cells undergo the slow response b/c they don’t have fast Na+ channels. Instead, the Ca2+ current is responsible for their depolarization (initiated first by If current at Phase 4), and the Ca2+ are slow channels.
ERP = effective refractory period (same as absolute refractory period)
RRP = relative refractory period
What is responsible for maintaining resting Vm in cardiac cells? Do we consider Na+ current when setting resting Vm in cardiac cells? If not, how is Na+ current involved in membrane potential?
At phase 4 = resting Vm set by the Inward Rectifying K+ current
Don’t consider Na+ current for resting Vm in cardiac cells b/c K+ current = high; external Na+ concentration determines peak membrane potential
Which currents are involved in AP propagation in pacemakers and at which phases are they active?
If
Ica
Ik
What is the effect of Ina in Ventricular Ap propagation? What happens when you add TTX?
What are the effects of Ica and Ik on ventricular AP?
Ina = fast Aps; when Ina is reduced, fast APs get converted to slow APs(in which the upstroke will then be due to Ca2+ channels)
TTX blocks Na channels and reduces Na conductance
Ica effect: responsible for Ap plateau
Ik: repolarizes membrane; blocking K+ channels prolongs Aps
Describe pacemaker depolarization. What is the role of I funny channels? During which phase are these channels active?
Due to inward current via I funny channels. Channels are slowly activated and drive Vm towards threshold.
Start activating at phase 4 of SA nodal action potentials
In which situations would the cardiac AP be slower?
What is the order of the speed on conduction in the heart and why?
Fewer Na+ channels (e.g. using TTX or another Na+ channel blocker)
Fewer Ca2+ channels activated in SA/Av node
If threshold is more positive
Purkinje fibers>Atria + Ventricles>SA/AV nodes
What is the effect of cycle length on the propagation speed of an AP? How are cycle lengthand Heart Rate related?
The faster the heart beat, i.e. the shorter the cycle, the faster the AP
HR and cycle length: shorter cycle length = faster HR
On an EKG, what do a P wave, QRS complex, and T wave represent?
P wave = atrial depolarization
QRS complex = ventricular depolarization
T wave = ventricular repolarization
Describe the role of NE/E (sympathetic system) on pacemaker AP
NE/E = activate Adenylyl cyclase >> increases cAMP >> stimulates If and Ca channels >> increase in inwards If and Ica current >> faster depol of SA/AV nodal cells >> faster AP= faster pacemaker
How do catecholamines like isopterenol increase contractility?
They increase Ca2+ conductance (increase in cAMP >> PKA activated >> add P to L type Ca2+ channels >> increase Ca2+ conductance)
Describe the effect of the parasympathetic system (cholinergic agonists i.e. ACh) on pacemaker APs
2 ways: increased ACh >> activates Gs beta and gamma subunits >> activates Ik(ach) channels >> increased outward current (less inward current = hyperpolarization in SA/AV nodal cells) >> slower depolarization b/c threshold is now more positive (closer to reversal potential for Ik)
Define an arrhythmia. What are the categories of arrhythmias discussed?
Arrhythmia: any rhythm that’s not a normal sinus rhythm
Conduction abnormalities + Abnormal automaticity
Types of Conduction abnormalities discussed
1st degree heart block
2nd degree heart block (Mobitz Type I and II)
3rd degree heart block
Bypass conduction
1st degree heart block. How do you id it on an EKG and what does that mean in terms of AP propagation?
Prolonged PR interval. Slowing of action potential.
2nd degree HB. How do you ID it on an EKG/how is it different from 1st degree Av block? What’s the pattern?
Progressive lengthening of PR interval. 3rd QRS complex dropped. Only some APs propagated; Pattern = Regularly irregular
3rd degree HB. How do you ID it on an EKG?
Atria and ventricles contract independently of each other. P waves and QRS complexes dissociated.
Bypass conduction. How does this happen and how can you ID this on an EKG?
Abnormal fast accesory conduction pathway from RA to ventricle (bypasses AV node) >> early depolarization of ventricles
Shorter PR interval; widened QRS complex with presence of delta wave
Which abnormal automaticity is this? How do you know?
Tachycardia
Shorter P-P interval
Which abnormal automaticity is this?
Bradycardia
Longer P-P intervals (slow HR)
How do you tell the difference between premature atrial and ventricular depolarizations?
Premature atrial depolarization: 2nd P wave is early and obscures T wave
Premature ventricular depolarization: 3rd QRS complex = early and bizarre
Which tachycardia is this? How do you know?
Supraventricular tachycardia. No P wave, only QRS complexes.
Which tachycardia is this? How do you know?
Ventricular tachycardia
Which automaticity abnormality is this? How do you know?
Atrial fibrillation
No P wave, irregularly spaced QRS complexes; irregularly irregular heartbeat
Which abnormal automaticity is this? How do you know? Why is this abnormality particularly concerning?
Ventricular fibrillation
No discernible rhythm. Blood isn’t pumped from the heart so its fatal if not CPR or defibrillation is given
Which abnormality is this? (hint: we talked about it in small group but not in lecture)
Atrial flutter. Sawtooth pattern.
Define early after-depolarization. What is this caused by?
Instead of getting back down to rest (i.e. Phase 4), a new AP starts firing midway through Phase 3 (start depolarizing again)
Likely due to reactivated Ca2+ channels
Describe how EADs can lead to a salvo of APs
Explain how Delayed afterdepolarizations occur
Occur when HR is high (cycle length is small)
When Na+/K+ pump is inhibited, NCX reverses direction and brings Ca2+ inside the cell
What are the types of blocks discussed in class?
Bidirectional block
Unidirectional block
Complete block
Describe each of the blocks
Bidirectional block: wave can’t travel to the other branch, or back to the S bundle
Complete block: wave doesn’t reach either branch (may result in V fib?)
Unidirectional block: wave can’t travel to one branch but retrograde wave from the other branch can go back to S bundle (may result in WPW syndrome?)
Describe Long QT syndrome
What are the variations of Long QT syndrome (i.e. which channels/currents are affected)?
Abnormal rhythm disorder
Widened QT interval - takes longer to repolarize b/c of reduced Ikr current (either via mutations in HERG channels or using HERG channel inhibitor drugs)
Romano Ward syndrome: reduced Ikr or Iks current
Timothy syndrome: Reduced Ica
