Lecture 11: Cardiac Electrophysiology Flashcards
Sequence of excitation in heart
SA node -> internodal pathways -> AV node -> bundle of His -> Purkinje fibers
Both atria contract then both ventricles contract.
SA node
(Normally) initiates depolarization in heart; R atrium near sup. vena cava. Pacemaker for entire heart, so discharge rate = heart rate
AV node
Node linking atrial/ventricular depolarization. Propagation is relatively slow, creating delay to allow atrial contraction to finish first. Only electrical connection between atria/ventricles. Has its own spontaneous pacemaking, but is slower than SA.
Differences in myocardial APs (contractile)
No immediate repolarization after Na+ inactivation; first partial repolar. due to special transient K+ channels then prolonged plateau ~0 mV
Mechanisms for prolonged depolar. plateau in cardiac APs
- Brief K+ channel closure; permeability goes below resting
- Large increase in Ca++ permeability; main difference vs sk. muscle
L-type Ca++ channels
Aka DHPRs; mediate cardiac AP plateau. Stim. by memb. depolar. to open, but much much slower vs. Na+ channels. L = long-lasting. Eventually inactivates to allow repolarization along w/ other delayed K+ channel opening to complete repolar.
Nodal cell APs (conducting, not contractile)
Pacemaker cells have no steady RMP; instead, gradual depolarizations occur spontaneously to threshold. Mediated by slower Ca++ channels, NOT Na+; this is what causes slower AP propagation across nodal cells i.e. in AV node. Repolar. w/ Ca++ closing, K+ opening
Ion channel mechanisms for pacemaker potentials
- Progressive K+ permeability reduction
- F-type Na+ channels
- T-type Ca++ chanels
Progressive K+ permeability reduction (pacemakers)
K+ channels opened from previous AP gradually close, slowly depolar. membrane. Some K+ channels ACh activated to slow SA node firing
F-type Na+ channels
Aka hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Non-specific cation channels (mainly Na+) that open at NEGATIVE memb. potential. Can be ligand gated for HR control
T-type Ca++ channels
Contributes Ca++ influx, last depolar. boost in pacemaker cells. T = transient
Automaticity
Spontaneous, rhythmic self-excitation. Pacemaker slope depends on how quickly threshold is reached. Neurons/hormones change slope from inherent 100 bpm
Ectopic pacemakers
When non-SA node cells manifest their own rhythm, e.g. AV conduction disorder -> vent. become out of sync with their own slow autorhythmic cells
ECG features
- P-wave - atrial depolar.
- QRS complex - vent. depolar.
- T wave - vent. repolar.
Excitation-contraction coupling in cardiac cells
Ca++ from L-type channels stimulates SR Ca++ release via RyRs; contraction ends w/ Ca++ ATPases, Na+/Ca++ antiporters. Same X-bridge cycling as sk. muscle. Ca induced Ca release
Refractory period of heart
Cardiac muscle doesn’t have tetanus since blood filling can only occur during relaxation. Caused by long absolute refractory period of cardiac muscle due to Na+ channel inactivation.
Cardiac muscle syncytium
Cardiomyocytes are electrically coupled at intercalated discs. Linked via gap junctions and myocyte bifurcations (branching)
Cardiac troponins
Same functions as sk. muscle, just w/ cardiac isoforms (cTnI, cTnC, cTnT). Ca++ release usually doesn’t saturate cardiac troponins, allowing force modulation.
2 types of cardiomyocytes
- Contractile (>99%)
- Electrical (autorhythmic + conducting, <1%)
Dromotropy
Velocity of conduction through heart; fastest in His-Purkinje fibers (vent. contracts efficiently/coordinated from bottom to top
Cardiac AP process
Phase 0: Stable RMP, activation -> fast Na+ depolar. then inactivat.
Phase 1: Brief rapid repolar. via Na+ inactiv., transient K+ efflux gate opening
Phase 2: Memb. potential plateau; slow L-type Ca++ open + slow rectifier K+ efflux open
Phase 3: Repolar; L-type Ca++ close, slow + fast rectifier K+ open
Phase 4: Return to RMP; K+, Na+, Ca++ balance
SA node AP process
No plateau, no RMP, automaticity
Slow F-type Na+ depolar -> T-type Ca++ influx -> L-type Ca++ @ threshold -> delayed K+ rectifier repolar.
Types of heart rate control
Chronotropic: increase/decrease heart rate
Dromotropic: increase/decrease AV node conduction speed
Ionotropic: increase/decrease contractile strength
Lusitropic: increase/decrease relaxation speed
Sympathetic innervation of the heart
-SA node (chronotrop.)
-AV node (dromotrop.)
-Contractile cells (ionotrop.)
NE -> β1 receptor GPCRs -> increase F-type Na+, T-type Ca++ current on SA node
Parasympathetic innervation of the heart
Parasymp. vagus nerve -> SA node, AV node
Little to no effect on contractile cells
ACh -> M2 receptor GPCRs -> delayed T-type Ca++ opening, K+ opening to hyperpolar. -> decrease SA prepotential slope + hyperpolar. membrane
ANS SA node innervation
SA node innervation changes slope of prepotential, which determines how quickly threshold is reached -> HR control
Interval-duration relationship
For stronger heart contractions, AP duration becomes shorter in order to maintain adequate filling time i.e. lusitropic effect required
Isoproterenol
Non-selective β agonist:
1. Increases plateau voltage via L-T Ca C phosphorylation
2. Decrease plateau duration by L-T CC open time reduction by high Ca++
Phospholamban
Regulates Ca++ resequestration; lusitropy depends on this Ca transport
