Lecture 11: Cardiac Electrophysiology

Question 1

Sequence of excitation in heart

Answer 1

SA node -> internodal pathways -> AV node -> bundle of His -> Purkinje fibers
Both atria contract then both ventricles contract.

Question 2

SA node

Answer 2

(Normally) initiates depolarization in heart; R atrium near sup. vena cava. Pacemaker for entire heart, so discharge rate = heart rate

Question 3

AV node

Answer 3

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.

Question 4

Differences in myocardial APs (contractile)

Answer 4

No immediate repolarization after Na+ inactivation; first partial repolar. due to special transient K+ channels then prolonged plateau ~0 mV

Question 5

Mechanisms for prolonged depolar. plateau in cardiac APs

Answer 5

1. Brief K+ channel closure; permeability goes below resting
2. Large increase in Ca++ permeability; main difference vs sk. muscle

Question 6

L-type Ca++ channels

Answer 6

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.

Question 7

Nodal cell APs (conducting, not contractile)

Answer 7

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

Question 8

Ion channel mechanisms for pacemaker potentials

Answer 8

1. Progressive K+ permeability reduction
2. F-type Na+ channels
3. T-type Ca++ chanels

Question 9

Progressive K+ permeability reduction (pacemakers)

Answer 9

K+ channels opened from previous AP gradually close, slowly depolar. membrane. Some K+ channels ACh activated to slow SA node firing

Question 10

F-type Na+ channels

Answer 10

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

Question 11

T-type Ca++ channels

Answer 11

Contributes Ca++ influx, last depolar. boost in pacemaker cells. T = transient

Question 12

Automaticity

Answer 12

Spontaneous, rhythmic self-excitation. Pacemaker slope depends on how quickly threshold is reached. Neurons/hormones change slope from inherent 100 bpm

Question 13

Ectopic pacemakers

Answer 13

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

Question 14

ECG features

Answer 14

1. P-wave - atrial depolar.
2. QRS complex - vent. depolar.
3. T wave - vent. repolar.

Question 15

Excitation-contraction coupling in cardiac cells

Answer 15

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

Question 16

Refractory period of heart

Answer 16

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.

Question 17

Cardiac muscle syncytium

Answer 17

Cardiomyocytes are electrically coupled at intercalated discs. Linked via gap junctions and myocyte bifurcations (branching)

Question 18

Cardiac troponins

Answer 18

Same functions as sk. muscle, just w/ cardiac isoforms (cTnI, cTnC, cTnT). Ca++ release usually doesn’t saturate cardiac troponins, allowing force modulation.

Question 19

2 types of cardiomyocytes

Answer 19

1. Contractile (>99%)
2. Electrical (autorhythmic + conducting, <1%)

Question 20

Dromotropy

Answer 20

Velocity of conduction through heart; fastest in His-Purkinje fibers (vent. contracts efficiently/coordinated from bottom to top

Question 21

Cardiac AP process

Answer 21

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

Question 22

SA node AP process

Answer 22

No plateau, no RMP, automaticity
Slow F-type Na+ depolar -> T-type Ca++ influx -> L-type Ca++ @ threshold -> delayed K+ rectifier repolar.

Question 23

Types of heart rate control

Answer 23

Chronotropic: increase/decrease heart rate
Dromotropic: increase/decrease AV node conduction speed
Ionotropic: increase/decrease contractile strength
Lusitropic: increase/decrease relaxation speed

Question 24

Sympathetic innervation of the heart

Answer 24

-SA node (chronotrop.)
-AV node (dromotrop.)
-Contractile cells (ionotrop.)
NE -> β1 receptor GPCRs -> increase F-type Na+, T-type Ca++ current on SA node

Question 25

Parasympathetic innervation of the heart

Answer 25

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

Question 26

ANS SA node innervation

Answer 26

SA node innervation changes slope of prepotential, which determines how quickly threshold is reached -> HR control

Question 27

Interval-duration relationship

Answer 27

For stronger heart contractions, AP duration becomes shorter in order to maintain adequate filling time i.e. lusitropic effect required

Question 28

Isoproterenol

Answer 28

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++

Question 29

Phospholamban

Answer 29

Regulates Ca++ resequestration; lusitropy depends on this Ca transport