Cardiac Electrophysiology Flashcards
(23 cards)
What is Resting Membrane Potential (RMP) in Excitable Cells?
Neuron: ~ -70 mV
* Skeletal Muscle: ~ -95 mV
* Cardiac Ventricular Muscle: ~ -85 mV
* Determined primarily by K⁺ permeability (100x more permeable to K⁺ than Na⁺ at rest)
* Maintained by Na⁺/K⁺ ATPase pump:
* 3 Na⁺ out / 2 K⁺ in
* Prevents cell swelling due to osmotic Na⁺ influx
Contributors:
* Ion Gradients: High K⁺ inside, high Na⁺ outside.
* K⁺ Leak Channels (K1): Major determinant of resting potential due to much higher permeability to K⁺ than Na⁺.
* Na⁺/K⁺ ATPase: Maintains gradients (3 Na⁺ out, 2 K⁺ in). Prevents osmotic swelling by expelling Na⁺ and restoring ionic balance.
What is phases of Ventricular Contraction?
Cardiac Ventricular Action Potential (Contractile Cells)
Consists of 5 phases: SA Node is Pacemaker of cell
1. Phase 4 (Resting):
* K1 leak channels maintain RMP.
2. Phase 0 (Depolarization):
* Fast voltage-gated Na⁺ channels open → rapid Na⁺ influx.
* Phase 1 (Initial Repolarization):
* Transient K⁺ (Kto) and Cl⁻ channels open briefly → minor repolarization.
3. Phase 2 (Plateau):
* L-type Ca²⁺ channels open → Ca²⁺ influx.
* Delayed rectifier K⁺ (KS) channels open → K⁺ efflux.
* Net zero charge → plateau (sustained contraction).
4. Phase 3 (Repolarization):
* Ca²⁺ channels close, but K⁺ channels stay open → repolarization.
* K1 channel de-rectifies and resumes K⁺ efflux.
🟡 Key Concept: Plateau allows time for ventricular contraction and refilling—essential for adequate stroke volume.
📝 Key Concepts:
* Plateau (Phase 2) is crucial for prolonged contraction and effective ejection of blood.
* Absolute refractory period lasts through early Phase 3 → prevents tetany.
* Relative refractory period during late Phase 3.
What is phases of Nodal cell contraction?
Nodal Action Potential (SA & AV nodes)
Pacemaker cells have a different AP structure:
* No stable RMP → slow diastolic depolarization
1. Phase 4:
* Funny (If) Na⁺ channels open due to hyperpolarization.
* Late Phase 4: T-type Ca²⁺ channels contribute.
2. Phase 0 (Depolarization):
* L-type Ca²⁺ channels open → Ca²⁺ influx (slower than Na⁺).
3. Phase 3 (Repolarization):
* K⁺ channels open → efflux → hyperpolarization → triggers next cycle.
🟡 No Phases 1 or 2.
What is phases of Purkinje Fibre contraction?
Purkinje Fibers
* Share features of both contractile and pacemaker cells:
* Fast Na⁺-dependent Phase 0 (like ventricles)
* Funny channels → very slow pacemaker activity
* Long diastolic depolarization
* Fastest conduction velocity due to large fiber diameter and abundant Na⁺ channels
How does the Autonomic Nervous System (sympathetic and parasympathetic) effect depolarization and repolarization?
🧠 Sympathetic (NE → β1 receptors):
* ↑ HR by:
* ↑ slope of Phase 4 (faster diastolic depolarization)
* ↑ funny channel and Ca²⁺ channel activity
🧠 Parasympathetic (ACh → M2 receptors via Vagus):
* ↓ HR by:
* ↓ funny and L-type Ca²⁺ activity
* Opens KAch channels → more K⁺ efflux → more negative membrane → slower depolarization
What are the 2 Refractory Periods?
- Absolute/Early (Effective) Refractory Period (ERP):
- From Phase 0 to ~1/3 of Phase 3 (no new AP possible)
- Relative Refractory Period:
- Late Phase 3 and Phase 4 (stronger-than-normal stimulus needed)
🛡 AV node: Longest refractory period → prevents atrial fibrillation from transmitting rapidly to ventricles
What is Conduction Velocity?
Determined by slope of Phase 0:
* Fastest: Purkinje fibers
* Slowest: AV node (due to fewer gap junctions and slower upstroke)
How does communication happen between cells?
Gap Junctions: Allow current flow → synchronized depolarization
* Conduction Pathway:
* SA node → atria → AV node → Bundle of His → bundle branches → Purkinje fibers → ventricles
- AV nodes have poor Gap junctions
Gap Junctions
* Type of cell-cell connection that allows direct ionic current flow.
* Formed by connexins, forming channels called connexons.
* Allow rapid spread of depolarization — critical for synchronized contraction.
* Most abundant in Purkinje fibers (fastest conduction).
* Sparse in AV node (contributes to slow conduction).
Desmosomes
* Mechanical adhesion structures.
* Hold cardiomyocytes tightly during contraction.
* Do not allow electrical conduction.
* Found in intercalated discs, along with gap junctions.
What are unique features of SA node compared to AV node?
📝 Unique Features:
* Automaticity (self-depolarizing).
* No plateau phase (no Phase 1 or 2).
* Controlled by autonomic nervous system:
* Sympathetic (β1-adrenergic): ↑ funny current → ↑ HR.
* Parasympathetic (M2 muscarinic): ↑ K⁺ via K_ACh → hyperpolarizes cell → ↓ funny current and HR.
Similarities vs Differences chart of Nodal, Ventricular and Purkinje Fibres:
What are the Calcium dependent and Sodium dependent action potentials?
Ca = SA node, AV node
Na= atrial myocytes, bundle of his, purkinje fibres, ventricular myocytes (voltage-gated Na channels)
What are the different types of Potassium (K) channels in cardiac cycle?
inward rectifier (Kir or K1) and the delayed rectifier K⁺ channels (Ks and Kr) — and how they function across the cardiac action potential phases.
⸻
🔹 K⁺ Channels in the Heart: Overview
There are several families of potassium channels in cardiac cells, and they contribute to setting the resting membrane potential, repolarization, and maintaining excitability.
⸻
🔸 1. Inward Rectifier Potassium Channels (Kir)
✅ K1 Channel (Kir2.x family)
* Function:
* Maintains resting membrane potential (Phase 4).
* Allows K⁺ to leave the cell when the inside is negative (resting).
* Open at rest, closed during depolarization.
* Not voltage-gated or ligand-gated: it’s a leak channel.
* High K⁺ conductance when the membrane is negative (e.g., −85 mV).
⚠️ Rectification
* “Inward rectification”: Sounds counterintuitive — it doesn’t mean K⁺ moves inward.
* It refers to the channel’s conductance pattern, not ion direction.
* At depolarized potentials, intracellular Mg²⁺ and polyamines block the channel.
* So during depolarization, K1 channel conductance decreases, limiting K⁺ efflux.
* Result: K⁺ flow is most efficient at negative voltages, helping maintain RMP but not active during repolarization.
⸻
🔸 2. Delayed Rectifier K⁺ Channels
These are voltage-gated and activated during phases 2 and 3 (plateau and repolarization).
✅ I_Ks (slow delayed rectifier)
* Slowly activates during plateau.
* Sustains outward K⁺ flow during phase 2 (plateau) and phase 3 (repolarization).
* More prominent under sympathetic stimulation (e.g., during stress, β-adrenergic stimulation ↑ I_Ks → shorter AP duration).
✅ I_Kr (rapid delayed rectifier)
* Rapidly activates and inactivates.
* Plays major role in initiating repolarization during phase 3.
* Target for many anti-arrhythmic drugs (Class III) and responsible for long QT if dysfunctional (e.g., in Long QT syndrome).
⸻
🔸 3. Other K⁺ Channels
✅ Ito (transient outward K⁺)
* Phase 1: short-lived, causes brief initial repolarization after Na⁺ spike.
* Seen mainly in ventricular myocytes.
✅ K_ACh (Acetylcholine-activated K⁺ channels)
* Present in nodal cells.
* Activated by parasympathetic stimulation (M2 receptors via vagus nerve).
* Increases K⁺ efflux → hyperpolarizes nodal cells → slows HR.
🔸 Clinical Relevance
* K1: Target in arrhythmias where resting potential is destabilized.
* IKr: Blocked by some drugs → QT prolongation → Torsades de Pointes.
* IKs: Upregulated by sympathetic stimulation (β1) → shortens action potential duration to accommodate faster HR.
Why is there a plateau in Phase 2 of the Ventricular Action Potential?
The plateau in Phase 2 is a unique feature of cardiac ventricular and Purkinje action potentials (not seen in neurons or skeletal muscle).
📍 What causes the plateau?
It is due to a balance of inward and outward currents:
* Inward current:
* L-type Ca²⁺ channels (I_Ca,L) open during depolarization.
* They allow Ca²⁺ to enter the cell slowly and steadily.
* Outward current:
* Delayed rectifier K⁺ channels (I_Ks, I_Kr) open, letting K⁺ leave the cell.
These two opposing currents cancel each other out, creating a stable, prolonged depolarized state — this is the plateau.
📌 Why is this important?
* It allows Ca²⁺ influx, which triggers calcium-induced calcium release from the sarcoplasmic reticulum, leading to ventricular contraction.
* The plateau ensures synchronous, strong contraction and prevents tetany in the heart (which must relax to refill with blood).
What is the difference between events in Phase 1 and Phase 2?
✅ Phase 1: Early Repolarization
* After the peak of Phase 0, the fast Na⁺ channels close (they inactivate, not just close).
* Two key currents:
1. Kto (transient outward K⁺ current):
* Briefly opens and allows a small amount of K⁺ to exit the cell.
* Causes a slight dip in the membrane potential.
2. ICl (Cl⁻ influx):
* Chloride enters, further contributing to slight repolarization.
* Both Kto and ICl are transient — they inactivate quickly.
* No Ca²⁺ yet — L-type Ca²⁺ channels haven’t fully opened.
⸻
✅ Phase 2: Plateau
* Now the L-type Ca²⁺ channels are open:
* Ca²⁺ slowly enters the cell → sustains a depolarized state.
* Important for triggering muscle contraction (via SR calcium release).
* At the same time:
* Delayed rectifier K⁺ channels (IKs and IKr) begin to open → K⁺ leaves the cell.
* Result: There’s a balance between inward Ca²⁺ and outward K⁺ → no net voltage change → plateau.
⸻
🔍 Why does the plateau occur only in ventricular myocytes (not neurons or nodal cells)?
Because:
* Ventricular cells express L-type Ca²⁺ channels prominently during the AP.
* Nodal cells also use L-type Ca²⁺, but they lack:
* Fast Na⁺ channels (so no Phase 0 spike),
* Prominent Phase 2, because nodal APs are meant for timing, not contraction.
What is the Diastolic Depolarization phase in SA nodes also know as?
Pacemaker Potential
Does KACh close funny channels and L-type Ca²⁺ channels in nodal cells?
📍 KACh channel (G-protein–coupled inward rectifier K⁺ channel)
* Activated by acetylcholine from parasympathetic vagus nerve.
* Opens and increases K⁺ efflux.
* Hyperpolarizes the membrane (more negative inside).
📌 Effects on pacemaker cells:
1. Funny current (If):
* Hyperpolarization normally activates If, but KACh causes stronger hyperpolarization and slows the rate of depolarization by making the membrane more negative.
* Net effect: Slower rise → slower HR.
2. L-type Ca²⁺ channels:
* Hyperpolarization delays the membrane from reaching threshold to open L-type channels.
* Also, M2 receptor signaling via Gi protein directly inhibits L-type Ca²⁺ channel activity.
* So, less Ca²⁺ influx, weaker depolarization.
🔍 Where does this occur?
* Both SA and AV nodes:
* SA node: ↓ heart rate (negative chronotropy).
* AV node: ↓ conduction velocity (negative dromotropy).
What phases are involved in AV conduction?
🔹 Atrioventricular (AV) Node Action Potential
✅ 1. Slower Diastolic Depolarization Compared to SA Node
* Diastolic depolarization = gradual rise in membrane potential during Phase 4, bringing the cell to threshold.
* In the AV node, this slope is shallower than in the SA node, meaning:
* Takes longer to reach threshold → slower intrinsic heart rate (~40–60 bpm vs. SA node ~60–100 bpm).
* This is due to less activity of funny channels (If) and weaker inward Ca²⁺ currents.
⸻
✅ 2. Absence of Fast Sodium Channels
* No fast Na⁺ channels (like ventricular myocytes have).
* Why? Nodal cells do not express voltage-gated fast Na⁺ channels.
* Therefore, Phase 0 (depolarization) is Ca²⁺-dependent, via L-type Ca²⁺ channels.
* This gives the AV node a slow conduction velocity, which is important for delaying ventricular contraction and allowing atrial emptying.
⸻
✅ 3. Channels Same as SA Node
Yes — SA and AV nodes share the same set of ion channels:
* Funny channels (If): Open when hyperpolarized → Na⁺/K⁺ current → initiate Phase 4.
* T-type Ca²⁺ channels: Open briefly during late Phase 4 to help reach threshold.
* L-type Ca²⁺ channels: Open during Phase 0 → main depolarizing current.
* K⁺ channels: Open during Phase 3 → repolarization.
* KACh channels: Opened by vagal stimulation → slows depolarization and HR (via M2 receptors).
So, both nodes use:
* Ca²⁺ instead of Na⁺ for depolarization.
* Funny channels for automaticity.
* But: AV node has less density and activity, so it’s slower.
⸻
✅ 4. L-Type Calcium Channels
* These open once the threshold is reached.
* Responsible for Phase 0 (depolarization) in the AV node.
* Slower opening and closing → slow upstroke of action potential.
* The same channels are used in SA node, but they’re weaker in the AV node.
Which Has a Shorter Plateau: Atria or Ventricle?
Why Is the Atrial Plateau Shorter?
- Weaker Ca²⁺ Current in Atria
- The L-type Ca²⁺ channels in atrial myocytes are less active than in ventricular myocytes.
- Less Ca²⁺ influx during Phase 2 → shorter plateau duration.
- Stronger K⁺ Currents in Atria
- K⁺ channels (like IKur, ultra-rapid delayed rectifier K⁺ current) are more active in atria, causing:
- Faster repolarization.
- Shorter action potential duration.
- Thinner Muscle Mass
- Atria have thinner walls than ventricles.
- They don’t require long, sustained contraction like the thick ventricles do, so a long plateau is not physiologically necessary.
The ventricular plateau (Phase 2) is longer because ventricular contraction must be sustained to generate enough pressure to eject blood into the systemic and pulmonary circulation.
What does Conduction Velocity depends on?
- Cell diameter and Resistance
AV node cells have the smallest diameter compared to any of the cells in the heart, so conduction through AV node is the slowest.
Purkinje fibers have the largest cell diameter and fastest conduction - Upstroke amplitude (amplitude of phase 0)- influences conduction velocity
The bigger the amplitude, the faster the conduction
AV node – small amplitude- Ca2+ AP- contributes to slow conduction in the AV node
Purkinje fibers- very high density of fast Na channels- Phase 0 amplitude is large upstroke- contributing to fast conduction. - Speed of Upstroke:
A fast upstroke rapidly raises the transmembrane potential during phase 0 toward positive levels.
Fast upstroke is due to rapid movement inward of Na+ ions. As a result, Na+ ions quickly reach the vicinity of the gap junctions and move through them to the next cell.
A large dv/dt or fast upstroke during phase 0 is associated with fast cell-to-cell conduction.
Slow in AV node, fast in Purkinje fibers
Purkinje Fibers: What They Have A Lot of vs. What They Lack?
Purkinje fibers are built for speed:
* Fast conduction due to:
* Lots of Na⁺ channels
* Large diameter
* Many gap junctions
But they’re not meant to lead the rhythm:
* Slow spontaneous depolarization → not dominant pacemakers
* If (funny current) is present but very slow
⸻
🧠 Key Takeaway:
Purkinje fibers = fastest conductors, not fastest pacemakers
Lots of Na⁺ channels + gap junctions = high conduction velocity
Slow pacemaker activity = only take over if SA/AV node fails
Why Do Ca²⁺ Channel Blocking Drugs Decrease AV Node Conduction Velocity?
🔸 1. AV Node Physiology Basics:
* The AV node does not use fast Na⁺ channels for Phase 0 (upstroke) like atrial or ventricular muscle.
* Instead, it relies on L-type Ca²⁺ channels to depolarize:
* Phase 0 = Slow depolarization due to Ca²⁺ influx through L-type calcium channels.
* This makes the AV node a slow-conducting structure by nature.
⸻
🔸 2. What Happens in Phase 0?
* Normally: Once the AV nodal cell hits threshold, L-type Ca²⁺ channels open, and Ca²⁺ enters slowly → causes slow, small upstroke.
* Conduction velocity is determined by the slope and amplitude of this upstroke.
* A steeper slope → faster conduction
* A flatter slope → slower conduction
⸻
🔸 3. What Do Ca²⁺ Channel Blockers Do?
* Drugs like verapamil or diltiazem block L-type Ca²⁺ channels.
* This results in:
* ❌ Less Ca²⁺ entry
* ⬇️ Smaller upstroke (lower amplitude)
* ⬇️ Slower rate of rise of Phase 0
* ⬇️ Conduction velocity through the AV node
⸻
🔸 4. Why This Matters Clinically:
* Used in rate control for atrial fibrillation/flutter:
* AV node is the “gatekeeper” between atria and ventricles.
* Slowing AV node conduction → prevents too many impulses from reaching the ventricles → prevents dangerously fast HR.
** AV node has a long refractory period also (helps protect ventricles against AFib)
Diagram of Adynelate Cyclase, cAMP, funnt channels, ATP and Autonomic NS:
Know these terms:
- Increase in Heart rate (+ve chronotropic)
- Increase in Force of contraction (+ve ionotropic)
- Increase in Excitability (+ve bathmotropic)
- Increase in Conductivity (+ve dromotropic)
