In my work as an instructor/tutor for the USMLE Step 1, one of the most common requests is to discuss antiarrhythmics. By the end of this USMLE Step 1 lesson, you will be able to answer the following questions:
- What would be the effects of class I antiarrhythmics on cardiac depolarization? Why? Nodal, non-nodal, or both?
- What would be the effects of class III antiarrhythmics on ventricular myocyte action potential? Why?
- Class III antiarrhythmics – main effect on EKG intervals? Why? What does this increase the risk of?
- What would be the effects of class IA antiarrhythmics on cardiac depolarization? Why?
- What would be the effects of calcium channel blockers on heart rate? Why does this make sense?
- Calcium channel blockers would affect which EKG interval in particular? Why?
- What would be the overall effect of ACh on heart rate and conduction via the AV node? Why?
Note: this lesson builds on a previous lesson on ion channel physiology.
We will begin by considering ventricular myocyte action potentials, then move on to consider the special case of nodal tissue.
Ready for the recall-type USMLE Step 1 questions?
What effect would opening Na+ channels have on a cardiac cell’s membrane potential?
Depolarization (membrane potential more positive)
What effect would opening Ca++ channels have on a cardiac cell’s membrane potential?
Depolarization
What effect would opening K+ channels have on a cardiac cell’s membrane potential?
Repolarization (become more negative)
Ventricular myocyte action potential – how many phases are there? What are they?
5 total
Phase 0, 1, 2, 3, and Phase 4
On an EKG, the P-wave corresponds to what?
Atrial depolarization
On an EKG, the QRS complex corresponds to what?
Ventricular depolarization
On an EKG, the T wave corresponds to what?
Ventricular repolarization
Phase 0 – Which ion channel(s) open/close? Effects on overall membrane potential?
Voltage-gated Na+ channels open → depolarization
Phase 1 - Which ion channel(s) open/close? Effects on overall membrane potential?
Voltage gated Na+ channels close / voltage-gated K+ channels open → initial repolarization
Phase 2 – Which ion channel(s) open/close? Effects on overall membrane potential?
K+ still open, but voltage-gated Ca++ channels open → plateau phase (have K+ moving OUT, while Ca++ moves IN→ minimal net movement of charges)
Phase 2 – most closely corresponds to what on EKG? Why does this make sense?
ST segment
The ST segment is typically flat, which would make sense, since during the plateau phase, there is minimal change in the net membrane potential
Phase 3 – Which ion channel(s) open/close? Effects on overall membrane potential?
Even more K+ channels open (voltage-gated “slow” K+ channels), voltage-gated Ca++ channels closed → ventricular repolarization
Phase 3 – most closely corresponds to what on EKG?
T wave (ventricular repolarization)
NOTE: atrial repolarization also occurs, but is NOT typically seen on the EKG, as the atrium is much smaller, and the repolarization would be obscured by the presence of the large QRS
Phase 4 – Which ion channel(s) open/close? Effects on overall membrane potential?
K+ channels open → membrane potential at resting potential (negative)
Class I antiarrhythmics – affect what ion channel(s)/receptors?
Na+
IA, IB, or IC – which affects another ion channel? Which ion channel is this?
IA ALSO blocks K+ channels, in addition to Na+ channels
Wait!
I strongly recommend that you attempt to answer the final questions by yourself first, before looking at the answers. Remember, the USMLE Step 1 exam will test your ability to make connections on the spot. The more practice you have, the higher your score! Then, when you think you might know the answer (or are completely stumped), look at the answers below!
Ready for the recall-type USMLE Step 1 questions?
What would be the effects of class I antiarrhythmics on cardiac depolarization? Why? Nodal, non-nodal, or both?
Slows phase 0 depolarization in non-nodal tissue
Recall that nodal tissue does NOT use Na+ (only uses Ca++) in phase 0 depolarization
Class IC antiarrhythmics will slow down depolarization, flattening the slope of Phase 0. Note that Class IA will have similar effects on Phase 0 depolarization
What would be the effects of class III antiarrhythmics on ventricular myocyte action potential? Why?
Class III antiarrhythmics would slow Phase 3 repolarization, since K+ channels mediate this repolarization
Class III antiarrhythmics delay Phase 3 repolarization by blocking the K+ channels necessary for repolarization. Note that Class IA antiarrhythmics will have similar effects on Phase 3 repolarization, as they also block K+ channels.
Class III antiarrhythmics – main effect on EKG intervals? Why? What does this increase the risk of?
Prolonged QT interval
Slows repolarization, so will prolong time between QRS complex (ventricular depolarization), and T wave (ventricular repolarization).
This will increase risk of TORSADES DE POINTES (you MUST know this for Step 1)
What would be the effects of class IA antiarrhythmics on cardiac depolarization? Why?
Slow phase 0 in non-nodal tissue
Prolong QT interval (also blocks K+ channels)
Next, we move on to discuss nodal tissue.
Ready for the recall-type USMLE Step 1 questions?
Nodal tissue action potential – how many phases are there? What are they?
3 total
Phase 0, 3, and Phase 4
Phase 0 – Which ion channel(s) open/close? Effects on overall membrane potential?
Voltage-gated Ca++ channels open → depolarization
Phase 0 – why is the action potential determined by Ca++ channels, and not Na+ channels?
(This is a review from a previous article)
In order to activate Na+ channels generally in the heart, you must first REMOVE INACTIVATION from them (double-negative, I’m sorry). In order to remove inactivation, you must have a more negative membrane potential. This is ONLY possible in non-nodal tissue, because of the presence of the special K+ channel, called IK1.
In other words, nodal tissues HAS Na+ channels (oddly enough), but it does NOT use them, because the membrane potential does NOT become negative enough to remove inactivation of the Na+ channels.
Ca++ channels do not have this sort of regulation, and thus will be active in nodal tissue.
What is the next phase to occur following Phase 0?
Phase 3
Note there is NO phase 1 or 2 in nodal tissue
Phase 3 – Which ion channel(s) open/close? Effects on overall membrane potential?
Ca++ channel inactivation, K+ channels open → repolarization
Phase 4 – Which ion channel(s) open/close? Effects on overall membrane potential?
“Leaky” Na+ / Ca++ channels → slow depolarization
Phase 4 – what will happen eventually following slow depolarization? What Phase will this correspond to?
Slow depolarization via leaky Na+ and Ca++ channels → pass voltage threshold for voltage-gated Ca++ channel opening → depolarization (phase 0)
What special K+ channels are present in nodal tissue that are absent in ventricular tissue? What causes them to open, and what would be the effect?
In nodal tissue (both SA and SA nodes), there are special K+ channels called IKG channels. When ACh binds to these channels, they will open → K+ efflux → hyperpolarization
What is the normal pathway of conduction through the heart, starting with the SA node?
SA node → atrium → AV node → His Purkinje system → ventricles
When the conduction signal moves from SA node to atrium, what causes the atrial depolarization?
SA node will depolarize the atrial tissue surrounding it, since they are electrically connected
What structures allow for depolarization of the atrium in response to SA nodal depolarization? How?
Gap junctions.
Allows for direct connection of cytoplasm between adjacent cells. This allows for the direct transfer of ions (and thus the wave of depolarization) from one cell to the next.
What allows for depolarization of the AV node?
Gap junctions connecting it to atrial tissue allow for transfer of action potential from atrial tissue → AV node
What does normal sinus rhythm mean?
Rhythm originates in the SA node
What determines the heart rate assuming a normal sinus rhythm (i.e. the rhythm originates in the SA node)?
Slope of the phase 4 depolarization in the SA node
In other words, if the slope of the phase 4 depolarization is HIGHER → reach depolarization threshold FASTER → have MORE depolarizations in a given time period (i.e. heart rate ↑)
What determines the speed of conduction through the AV node?
Slope of the phase 0 depolarization through the AV node
Why does it make sense that it is phase 0 and NOT phase 4 depolarization that will determine this?
It is a question of HOW you reach the depolarization threshold
In the case of the SA node, phase 0 depolarization is reached because of SPONTANEOUS depolarization during phase 4. In other words, leaky Na+ and Ca++ channels → slow depolarization → reach depolarization threshold
In contrast, the AV node is depolarized directly following atrial depolarization. Note that this is NOT spontaneous, and is in fact triggered by the atrial depolarization itself.
Class II antiarrhythmics – affect what ion channel(s)/receptors?
β blockers
Class IV antiarrhythmics – affect what ion channel(s)/receptors?
Ca++ channel blockers
Wait!
I strongly recommend that you attempt to answer the final questions by yourself first, before looking at the answers. Remember, the USMLE Step 1 exam will test your ability to make connections on the spot. The more practice you have, the higher your score! Then, when you think you might know the answer (or are completely stumped), look at the answers below!
Almost there! Think about how nice it will be to finally understand the antiarrhythmics section in First Aid!!
What would be the effects of calcium channel blockers on heart rate? Why does this make sense?
HR ↓Slope of phase 4 depolarization ↓ → reach threshold slower → fewer depolarizations in a given time period → HR ↓
Calcium channel blockers would affect which EKG interval in particular? Why?
PR interval ↑ by slowing phase 0 depolarization
Takes longer for signal to travel between atrium (P wave) to ventricle (QRS complex), because conduction through the AV node is slower → interval between P and QRS (PR interval) ↑
What would be the overall effect of ACh on heart rate and conduction via the AV node? Why?
ACh binds IKG channels → K+ efflux ↑ → hyperpolarization → require more cation influx to get same level of depolarization → slow conduction through AV node and slow heart rate
What should you do next?
- Turn the narrative, “Pathogenesis to Presentation” questions into Anki cards by copy/pasting the question/answer into the “Front” and “Back” fields in Anki. Do the same for the fundamental facts that you were unfamiliar with, to maximize your chances of USMLE Step 1 success! Remember: the USMLE is a test of understanding, so the better you can understand these questions, the better your score!
- Add reverse cards when appropriate to your Anki cards
- Re-word the questions/explanations as desired, and BOLD the important text to make it easier to review in the future
- Learn something new? Something unclear? Comment below!
- If you liked this post, please consider sharing it on Facebook/Twitter! I judge the utility of these posts by the number of comments / shares they receive, so if you’d like more, or would like a particular topic addressed, please let us know!
Photos by: ZaaFari,Silvia3, and Kalumet.
12 Comments
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Hi Alec!
Pacemaker tissue = Nodal tissue: Does His-Purkinje system action potential have 5 phases (the same as Contractile tissue = Non-nodal tissue = Atria & Ventricles) since they do not have Automaticity (HCN channels)?
Hmm…that is a great question. I assume so? Like you mentioned, I don’t think the Purkinje system has automaticity, so I assume it would be like other non-nodal tissue.
Loved this! Thank you. Are your Anki decks build similarly? I mean do they flow with the same logic that builds?
Thanks so much! They are similar in the sense that they are pathogenesis to presentation, and try to explain the underlying logic/reasoning, but they aren’t broken down into so many parts, since I’ve found this to be a great technique for learning, but not a great technique for retention. They ARE built off the same model of using a basic principle to explain something else, like “Calcium channel blockers would affect which EKG interval in particular? Why?” There are sample cards you can download at yousmle.com/step1anki.
Thanks again for your comments!
Alec
thank a lot Alec!!You are a true inspiration!!
Of course – thank you so much for your kind words!
super fast brush up!!!!
thanx a lot alec, feel like im in total control of cardiac pharma!!!
Hi Chinni – thanks so much for the feedback! I’m glad it was helpful!! I look forward to hearing your feedback in the future, as well!!
Take care,
Alec
Well when you put it that way :)… Thank you for sharing your insights. The “light bulb” turned on several times. Understanding “why does this make sense” has been lacking in my approach to learning much of this material…. until now.
Forever grateful.
Dear Wisdom Seeker,
Thank you so much for your positive comments! I remember how much I struggled with this material when I studied for Step 1, and so if I was able to help in any way, I am grateful =)
Take care,
Alec
Gold. 🙂
Thank you so much!!