Cardiac AP and conduction system

[DSA] What are the three general types of cardiac action potentials

1. Non-pacemaker action potentials, AKA: fast response action potentials

   • rapid depolarization,

   • atrial and ventricular myocytes does this 

2. slow response action potentials

   • slower rate of depolarization

   • Found in SA and AV nodes

3. Specialized conducting cells found within the His-Purkinje system

   • Similar to fast response action potentials but EXHIBIT SPONTANEOUS DEPOLARIZATION

[DSA] List the Differences between Cardiac Action potentials and neural/skeletal muscle action potentials

1. APs are much longer in cardiac cells

2. The Role of Ca2+

   • Nerve/Muscle: depolarization = opening of fast sodium channels.

   • Cardiac Pacemaker Cells: Ca2+ are involved in initial depolarization phase

   • Non-pacemaker cells: Ca2+ influx prolongs duration of AP → plateau phase

[DSA] Describe What happen in each Phase in Non-Pacemaker AP

Phase 4: @ resting membrane voltage; K+ is leaking out; Fast-sodium channels/ L-type slow Ca2+ channels = closed → Na/Ca2+ not going in

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Phase 0:

• Threshold Reached @ -70 → Na+ conductance increases via fast Na channels → Depolarization

• K+ conductance decreased due to K+ channels closing

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Phase 1:

• Short Repolarization due to opening of transient outward K⁺ channel (K_to)

  • this is short lived

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Phase 2:

• @ same time as K+ efflux, Slow Inward Ca2+ influx is occuring via L-type Ca channels

  • opens @ about -40 mV

• Overall → plateau

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Phase 3:

• Repolarization due to increased K+ efflux coupled w/ inactivation of Ca2+ channels

1. [DSA] When does the effective refractory period occur in a non-pacemaker cell.

2. What is the mechanism?

3. Why is this beneficial?

ERP is during phase: 0,1,2,3 and early 4

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Mechanism:

• fast Na channels = inactivated following channel closing during phase 1 (see figure).

• They are not in their closed, resting (excitable) state until sometime after the membrane potential has fully repolarized

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Benefits:

• Prevents Multiple APs compounding → affects HR

  • @ high HRs, heart can’t fill adequately w/ blood → ventricular ejection decreases

[DSA] Describe the Transformation of non-pacemaker into pacemaker cells

In hypoxic events:

• membrane depolarizes → closes fast Na+ channels 

• @ -50mV → slow inward Ca2+ channels open → APs are possible

  • can display spontaneous depolarization and automaticity

[DSA] Describe the Phases of SA Node Action Potential (pacemaker action potentials)

Phase 4:

• slow, inward Na⁺ currents → Spontaneous depolarization

  • Called “funny” currents (I_f)

• @ -50mV → T-type Ca++ channel (T=transient) open → Ca2+ Enters

• @ -40mV → L-Type Ca2+ channels open (L= long-lasting) → Ca2+ enters

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Phase 0:

• Depolarization via L-type Ca++ channels

• Funny currents + T-type Ca++ channels are closed @ this time

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Phase 3:

• Repolarization via K⁺ channels opening

• L-type channels Closed

What are the Primary, Secondary, and Tertiary pacemaker cells

Primary: SA Node

Secondary: AV Node

Tertiary: Purkinje Fibers

***If SA Node fails, AV node take over; Purkinje takes over if AV fails***

***As you go from Primary → Tertiary, the intrinsic rate decreases***

Which specialized cardiac myocytes are specialized for rapid
and regulated conduction

1. Internodal Pathways (Right Atrium)

   • Conduct impulses from SA → AV 

2. AV Node Cells

   • Slow conduction → physiological delay between atrial and ventricular activation

3. Purkinje Cells (AV Bundle, Bundle of His, Purkinje Fibers)

   • rapid conduction → synchronized ventricular contraction

[REVIEW] Sequence of electrical activation in the heart

List out the phases of fast-response action potential

• Phase 0: Rapid depolarization
  

• Phase 1: Early partial repolarization
  

• Phase 2: Plateau phase
  

• Phase 3: Final repolarization
  

• Phase 4: Resting potential

Describe the two refractory periods present in cardiac myocyte

Absolute / Effective Refractory Period (ERP) (Vm > +30mV):

• phases 0, 1, 2, and early phase 3

• inactivation of voltage-gated Na⁺ channels via inactivation gate → block new APs regardless of strength

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Relative Refractory Period (RRP) (+30mV > Vm ≥ -90 mV):

• second half of phase 3 and ends before phase 4

• Requires stronger stimulation then usual

What is the significance of the Refractory Period?

Significance of the refractory period:

• Ensures that APs propagate in a unidirectional and
  coordinated manner through cardiac tissue.

• Prevents premature re-excitation of recently activated cells

  • maintain synchronized electrical activity

  • allowing impulses to travel efficiently

  • avoid chaotic conduction or reentry

List out the roles of K+ channels in cardiac electrophysiology? Clinical Importance?

K⁺ channels are essential for:

• Shaping the action potential waveform

• Controlling repolarization and refractory periods

• Maintaining resting membrane potential

• CLINICAL IMPORTANCE:

  • K⁺ channels are targets for many cardiac drugs
    used to treat arrhythmias and regulate heart rate and rhythm

Describe K_AcH and K_ATP:

• Function?

• Mechanism?

KAch:

• primarily active in atrial myocytes and play a minimal role in ventricular cells

• open during late Phase 3 and early Phase 4 → increases K+ conductance → shortens atrial AP and hypolarizes membrane

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KATP:

• ATP-dependent K⁺ channels that link cellular metabolism to membrane excitability.

• Open when Low intracellular ATP levels →K⁺ efflux→ membrane hyperpolarization.

  • helps protect the heart during metabolic stress by reducing excitability and conserving energy.

List out the phases of pacemaker APs

Describe Funny Currents:

• AKA?

• Type?

• Why is it called funny?

Na+ inward current: Funny Current (If) Channels:

• Hyperpolarization-activated cyclic nucleotide-gated (HCN)

• are on selective cation channels permeable to Na⁺ and K⁺

  • Primarily Na

• Called Funny because:

  • activate during hyperpolarization

  • modulated by cyclic AMP (cAMP)

What are there none of @ SA/AV nodes (hint: channel)

NO fast Na+ channels in the SA and AV nodes

Describe the Refractory period in pacemaker cells as opposed to non-pacemaker cells

Refractory period in pacemaker cells:

• Refers to the continuous recovery of excitability during the action potential

  • around the early part of phase 4

• includes the time needed for ion channels to reset after repolarization is complete

• recovery of full excitability is a slower process than in "fast-response action potentials, which ensures a steady, regular rhythm

1. What is a normal HR called?

2. Define:

   • Tachycardia

   • Bradycardia

• Normal HR: normal sinus rhythm

• Tachycardia: HR > 100 bmp

• Bradycardia: HR < 60 bpm

[REVIEW] Regulation of the heart and vasculature via autonomic, hormonal, and local factors

1. In regards to the heart, what does parasympathetic innervation primarily influence?

2. What about sympathetic innervation?

Para: vagus nerve primarily innervates the SA and AV nodes, influencing heart rate.

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Sympathetic: mainly target cardiac muscle (controlling contractility),
with limited input to pacemaker cells

1. Describe how NE and AcH affect the heart

2. How do they interact w/ another?

NE:

• via B1-AR

• positive chronotropic (↑HR),

• positive dromotropic (↑conduction velocity)

• positive inotropic (↑contractile forces)

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AcH:

• via M2 receptors

• negative chronotropic,

• negative dromotropic,

• negative inotropic

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How NE and AcH interacts w/ each other:

• crosstalk between systems modulates cardiac activity by competing for second messengers (cAMP)

• Cardiac myocytes have adrenergic and cholinergic receptors

Describe how Autonomic input influences pacemaker activity

Autonomic input modulates this rhythm:

• Vagal input reduces SA node firing

• Sympathetic activation raises heart rate, especially during activity

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SA Node Also influenced by:

• hormones, ion concentrations, hypoxia, drugs, and age

1. Describe the mechanism on how the parasympathetic system influences pace maker cells

2. Net Effects?

Parasympathetic regulation: via M₂ receptors

• Postganglionic → AcH → M2 

  • Reduces cAMP:

    • ↓ If (funny current) → slower Phase 4 depolarization

    • ↓ ICa,L → reduces Ca²⁺ influx

    • Both above reduces steepness of Phase 4

  • ↑ IK,ACh → increases K⁺ efflux, hyperpolarizing the membrane

    • Hyperpolarizing membrane = maxing diastolic potential more negative

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Net Effects:

• Slower heart rate (SA node)

• Reduced conduction velocity (AV node)

• More negative maximum diastolic potential

• Less steep pacemaker potential slope

• Higher threshold for action potential initiation

1. Describe the mechanism on how the sympathetic system influences pace maker cells

2. Net Effect?

Sympathetic regulation: via β₁-adrenergic effects:

• Activates B1 → increases cAMP

  • ↑ If in SA node → steeper Phase
    4 depolarization

  •  ↑ Ca²⁺ current in myocardial
    cells

    • steeper Phase 4

    • lower threshold for action
      potential initiation

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Net Effect:

• Increased heart rate (SA node)

• Increased conduction velocity through the AV node

• More steep pacemaker potential slope

• Lower threshold for action potential initiation