6. Arrythmia Flashcards
(48 cards)
What is Atrial Fibrillation
-Rapid, irregular heartbeat
-Most common heart rhythm irregularity
-May cause blood clot formation
Name the sequence of sinoatrial node pacemaker potential
-Phase 4 (pacemaker potential)
-Phase 0 (depolarisation)
-Phase 3 (repolarisation)
Describe phase 4 of the sinoatrial node pacemaker potential
-The SA node lacks a stable resting membrane potential.
-Instead, the membrane potential gradually depolarizes due to the opening of funny (If) sodium channels, allowing Na⁺ influx.
-As depolarization progresses, T-type calcium channels open, allowing Ca²⁺ influx, further depolarizing the cell.
-The progressive depolarization eventually reaches the threshold (~-40 mV), triggering an action potential.
Describe phase 0 of the sinoatrial node pacemaker potential
-Once the threshold is reached, L-type calcium channels open, leading to a rapid Ca2+ influx and depolarisation
-This phase is slower than in ventricular myocytes, where fast Na+ channels dominate
Describe phase 3 of the sinoatrial node pacemaker potential
-As the membrane potential becomes more positive, L-type Ca2+ channels close, and K+ channels open, allowing K+ efflux
-The membrane repolarises back towards the most negative potential (-60mV) closing K+ channels and restarting the cycle
Describe the relationship between the SAN and the rhythm of the heart rate
-This automatic rhythmic depolarization of the SA node dictates heart rate, making it the primary pacemaker of the heart.
-Modulation by the autonomic nervous system can alter pacemaker potential dynamics, with sympathetic stimulation (β1-adrenergic activation) increasing firing rate and parasympathetic stimulation (via the vagus nerve and M2 receptors) slowing it down.
What mediates the funny current?
HCN gated channels
(hyperpolarisation activated cyclic nucleotide dependent nonspecific channels)
Name the phases of the ventricular myocyte action potential
-Phase 0 (rapid depolarisation)
-Phase 1 (initial repolarisation)
-Phase 2 (plateau phase)
-Phase 3 (repolarisation)
-Phase 4 (resting membrane potential)
Describe phase 0 and 1 of ventricular myocyte action potential
Phase 0: -Triggered by an action potential from adjacent cells
-Fast voltage gated Na+ channels open, causing a rapid influx of Na+ which depolarises the membrane to approximately +30mV
Phase 1: -Na+ channels inactivate, stopping further depolarisation
-Transient outward K+ channels (Ito) open briefly, allowing K+ efflux, causing a small drop in membrane potential
Describe phase 2, 3 and 4 of ventricular myocyte action potentials
Phase 2 (Plateau Phase):
-L-type Ca²⁺ channels open, allowing Ca²⁺ influx, which balances K⁺ efflux from delayed rectifier K⁺ channels.
-This maintains the plateau and triggers calcium-induced calcium release (CICR) from the sarcoplasmic reticulum, leading to contraction.
Phase 3 (Repolarization):
-L-type Ca²⁺ channels close, while K⁺ efflux (via delayed rectifier K⁺ channels) increases, leading to repolarization.
-The membrane potential returns to its resting state (~-90 mV).
Phase 4 (Resting Membrane Potential):
-The cell remains at ~-90 mV, maintained by inward rectifier K⁺ channels (IK1), while the Na⁺/K⁺ ATPase and Na⁺/Ca²⁺ exchanger restore ion gradients.
-The myocyte is ready for the next action potential.
Key features of ventricular myocyte action potentials
-Long duration (~200-300 ms) compared to neurons or skeletal muscle.
-The plateau phase prevents tetany, ensuring coordinated contraction and relaxation.
-Modulated by the autonomic nervous system, with β1-adrenergic stimulation increasing Ca²⁺ influx (stronger contraction) and parasympathetic activity having minimal direct effect.
Describe the molecular mechanism of sympathetic nerves affecting heart rate
-Sympathetic nerve terminals release noradrenaline, binding to β₁-adrenergic GPCR receptors
-This activates Gs protein which activates Adenylyl cyclase, producing cAMP, which activates PKA
-cAMP acts on HCN channels, and PKA acts on L-type calcium channels and delayed rectifier potassium channels
-The combined effects of increased If (faster depolarization), ICaL (enhanced depolarization), and IKs (faster repolarization) shorten the duration of the pacemaker potential.
Describe the action of cAMP on HCN channels
-cAMP directly binds to hyperpolarisation-activated cyclic nucleotide gated channels, increasing open probability
-This enhances the inward Na+ current (funny current) accelerating phase 4 of the SA node action potential
-Leading to positive chronotropy
Describe the action of PKA on L-type calcium channels
-PKA phosphorylates voltage gated Ca2+ channels, increasing influx during depolarisation
-This shortens the pacemaker potential and hastens the threshold for the next action potential
Describe the action of PKA on delayed rectifier potassium channels
-PKA phosphorylates K⁺ channels, increasing K⁺ efflux during repolarization.
-This facilitates quicker resetting of the pacemaker cells, preparing them for the next cycle.
Describe the net effect of noradrenalines effect on heart rate
-The combined effects of increased If (faster depolarization), ICaL (enhanced depolarization), and IKs (faster repolarization) shorten the duration of the pacemaker potential.
-This increases the frequency of action potentials in the SA node, leading to an increased heart rate (tachycardia)
Describe the molecular mechanism of parasympathetic nerves affecting heart rate
-Vagus nerve releases ACh, binding M2 GPCR muscarinic receptors on SAN cells
-These activate Gi protein (inhibiting Adenylyl cyclase) and activate Gprotein-gated inward rectifier potassium channels (GIRK)
-Lower cAMP reduces HCN activation, decreasing funny current leading to slower diastolic depolarisation, as well as decreasing phosphorylation of L-type Ca2+ channels
-GIRK channels are activated, increasing K+ efflux, hyper polarising the SAN
Describe the net effect of acetylcholine’s effect on heart rate
-Slower phase 4 depolarisation (due to decreased If and ICaL).
-More negative resting membrane potential (due to increased IKAch).
-Longer time to reach threshold → Fewer action potentials per minute → Reduced heart rate (bradycardia).
Describe the dominance of vagal tone to the heart
-At rest, the human heart is under a dominant vagal (parasympathetic) tone, meaning the parasympathetic nervous system exerts greater influence than the sympathetic nervous system over baseline heart rate.
-This results in a lower resting heart rate (typically 60–70 bpm) than the intrinsic pacemaker rate of the sinoatrial (SA) node (~100 bpm)
What are early afterdepolarisations? (EAD)
-Abnormal, spontaneous depolarisations
-Occuring during the repolarisation phase (phases 2 or 3) of the cardiac action potential
-Can contribute to arrhythmias, particularly in conditions of prolonged action potentials
Name and describe some mechanisms of early afterdepolarisations
-Delayed repolarisation, with calcium or sodium channels opening irregularly
-Prolonged depolarisation, L-type Ca²⁺ channels can reactivate.
adding an extra inward current during repolarisation.
-Some sodium channels stay open too long or reopen late → adds more positive charge, delaying repolarisation further and promoting EADs.
What are delayed afterdepolarisations? (DAD)
-Abnormal. spontaneous depolarisations
-Occur after full repolarisation (during phase 4)
-If any reach threshold, they can trigger ectopic action potentials and arrhythmias
Name and describe some mechanisms of delayed afterdepolarisations (DAD)
-SR leaks Calcium, triggering a small inward current (via the Na⁺/Ca²⁺ exchanger)
-β1-receptor stimulation → more calcium enters the cell = more likely to leak out SR and cause DADs.
-Certain drugs can lead to calcium overload or altered ion handling, eg digoxin
-If DADs reach threshold, they can generate premature action potentials, leading to ventricular or atrial arrhythmias
Describe the Vaughan Williams classification of antiarrhythmic drugs
Categorises drugs based on their primary mechanism of action:
-Class I: Na+ blockers
-Class II: Beta blockers
-Class III: K+ blockers
-Class IV: L-type Ca2+ blockers
