Download AV node and AV bundle.

ID639 - Cardiac Muscle action potentials and
heart excitation
LO1. Contrast the typical action potential in a ventricular muscle and a pacemaker cell.
LO2. Explain how ionic currents contribute to the five phases of the cardiac action
potential. Apply this information to explain differences in shapes of the action potentials
of different cardiac cells.
LO3. Explain what accounts for the long duration of the cardiac action potential and the
resultant long refractory period and what is the advantage of the long plateau of the
cardiac action potential and the long refractory period.
LO4. Explain the ionic mechanism of pacemaker automaticity, and identify cardiac
cells that have pacemaker potential and their spontaneous rate. Identify neural and
humoral factors that influence their rate.
LO5. Describe the normal sequence of cardiac activation (depolarization) and the role
played by specialized cells.
LO6. Explain why the AV node is the only normal electrical pathway between the atria
and the ventricles; describe the functional significance of slow conduction through the
AV node.
CV physiology References
Web sites:
www.cvphysiology.com; www.cvpharmacology.com (very good, particularly suitable
for the “PBL” course)
Textbooks:
• Linda Costanzo: Physiology (the shortest)
• David E. Mohrman, Lois Jane Heller: Cardiovascular Physiology
• Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine (standard
textbook of cardiovascular medicine, useful for PBL “tasks” )
• Guyton & Hall: Textbook of medical physiology, Chapters 5, 6, 9-24
• Revise the foundation module electrophysiology and circulation
Contact: M. Turcani, Physiology, room 331; [email protected]; Office hours:
Sunday at 2.00 p.m. (until needed)
LO1 – Cardiac action potentials have different shapes
A.
B.
C.
D.
E.
F.
SA-node
Atrial myocytes
AV-node
Ventricular myocytes
Purkynje fibers
Injured myocytes
 Shape of the action potential (AP ) is
determined by the ionic fluxes through
membrane channels.
 Fast AP (B, D, E): depolarization is rapid
via fast Na-channels
 Slow AP (A, C, F): depolarization is slow
via slow Ca-channels
 Duration of AP (triangular/ rectangular) is
determined by the balance between
depolarizing currents (sodium, calcium)
Abreviations: dV/dt: speed of depolarization
and repolarizing currents (potassium).
Vm: membrane potential
Ampl: action potential amplitude
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LO2 – Ionic currents that generate cardiac action
potentials – fast action potential
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Phase 0: rapid influx of Na+ (iNa) accounts for the steep
upstroke of the membrane potential (Vm)
Phase 1: cells repolarize rapidly to nearly 0 mV, because
of inactivation of iNa & concomitant activation of transient
outward K+ current (iKto).
Phase 2: Depolarization is prolonged (plateau) because
K+ permeability decreases (inactivation of iKto,
deactivation of iK1) and Ca2+ permeability increases
(activation of iCaL).
Phase 3: Repolarization progresses because
permeability for Ca2+ is decreasing & K+ permeability is
increasing. The efflux of K+ exceeds the influx of Ca2+. K+
channels involved in repolarization: delayed rectifier K+
channel (IK), inward rectifier K+ current (IK1)
Phase 4: Resting Vm is reached, membrane is
permeable mainly to K+ through iK1 and non-gated K+ 2pore channel (iK2P).
LO2 – Ionic currents that generate cardiac action
potentials – slow action potential
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Phase 0: Depolarizing current is carried by Ca2+
through the L-type Ca-channels (iCaL). Vm of -60mV
makes fast sodium channels inactive.
Phase 3: Repolarization occurs as K+ channels open
thereby increasing the outward, repolarizing K+
current (iK). At the same time, the L-type Ca++
channels close, calcium permeability decreases
Phase 4: spontaneous diastolic depolarization,
pacemaker potential: SA & AV nodal cells have an
instable resting Vm. When the Vm is about -60 mV,
HCN-channels (if) that conduct slow, depolarizing
inward Na+ current open and the potassium
equilibrium potential (-90mV) cannot be reached.
As the Vm reaches about -50 mV, T-type Ca-channels open (iCaT). As Ca2+ enter the cell
through these channels, they further depolarize the cell. At about -40 mV, L-type Ca channel
open and AP is generated. During phase 4 there is also a slow decline in the outward
movement of K+ contributing to the pacemaker potential.
LO3 – Absolute (ARP) and relative (RRP)
refractory periods
1
0
4
2
3
4
 ARP (phase 0,1,2,3 partly): no
AP could be generated
 RRP (phase 3 partly): deformed
AP are generated with stronger
than normal stimuli
 Mechanism: inactivation of Na& Ca channels
 ARP limits the frequency of AP
and contractions
 ARP prevents the reentry
 APs generated during the RRP resemble slow AP, (upstroke is slower,
amplitude is lower, duration is shorter). These premature AP are conducted
slowly and hence reentry is more likely to occur.
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LO4 – The rate (slope) of the phase 4 in pacemaker
cells sets the heart rate (chronotropic effects)
 Sympathetic stimulation opens
more HCN-channels and L-type
calcium channels what makes
phase 4 more steeper, threshold
(Th) is reached sooner – heart rate
increases (positive chronotropic
effect)
 Parasympathetic stimulation
reduces iHCN and iCa2+ what makes
phase 4 less steeper, Th is reached
later – hear rate declines (negative
chronotropic effect). Moreover,
opening of the acetylcholine
regulated K+-channels
hyperpolarizes SA-node cells. Thus,
more time is needed to reach the
threshold.
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LO5 – Excitatory and conductory system of the heart
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 Electrical impulses (AP) that activate
contraction are generated in pacemaker
Internodal tracts
cells.
SA-node
 SA node is the primary pacemaker, i.e. it
normally initiate depolarization (AP) that
activates all regions of the heart.
 SA node is the primary pacemaker
AV-node
because it depolarizes spontaneously at a
more rapid rate than any other areas of
the heart (60-100beats/min).
 AV node & AV bundle is the secondary
pacemaker with the intrinsic rate of 40 to
55 beats/min. I
 Tawara branches & Purkynje fibers are
the tertiary pacemaker producing AP at
rates of 25 to 40 beats/min (idioventricular
rhythm).
 Ectopic pacemakers (foci) are regions of the heart other than the sino-atrial node that
initiate action potentials.
LO5 – Spread of excitation over the atria
and the conductory system
 AP spontaneously generated in the SA node spread slowly (0.01 m/sec) inside the SA
node.
 AP are conducted over the atria via special internodal tracts at a more rapid rate (1
m/sec).
 The only electrical connection that links the atria and ventricles is the AV node and AV
bundle.
 Conduction velocity in the AV node is very slow (0.02-0.05 m/sec).
 When AP exit the AV node, they are converted back to the fast AP and travel further via
the bundle of Hiss (AV-bundle), which bifurcates into right and left bundle branches
(Tawara) .The left one divides into anterior and posterior fascicles. The bundle branches
descend on the endocardial surface and give off large-diameter Purkinje fibers.
 The large diameter of Purkynje fibers accounts in part for the great conduction velocity 4
m/s. In addition, Purkinje fibers have 5 times more fast Na-channels compared to other
myocytes and thus very high rate of depolarization. The broadly dispersed ramifications of
the His-Purkinje system and the rapid conduction within it result in depolarization of most
of the endocardial surfaces of both ventricles within several milliseconds.
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LO5 – Spread of excitation over the ventricles
 After the septum, the excitation sweeps down and around the anterior
free walls to the posterior and basal regions in an apex-to-base
direction.
 The posterobasal areas of the ventricles (the outflow tracts) are the last
to be activated.
 The activation action potentials move from endocardium to epicardium.
Excitation of the endocardium begins at sites of Purkinje-ventricular
muscle junctions and proceeds by muscle cell-to-muscle cell
conduction toward the epicardium with the conduction velocity of 1m/s.
 Repolarization begins in the epicardium (epicardial APs have shorter
duration than endocardial APs because they have stronger Ito current).
 Purkynje fibers are repolarized at the end of the recovery.
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3
LO6 – Electrophysiological properties of the AV node
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1. Conduction is very slow (0.02-0.05 m/sec) in the AV-node because
APs are slow and the nodal cells have small diameter. This makes
this area especially vulnerable to conduction block (AV block).
2. AV-node delays activation of the ventricles. This ensures that the
ventricles are relaxed at the time of atrial contraction and permits
optimal ventricular filling during the atrial contraction.
3. Relative refractory period is long in the AV-node. Therefore, AVnode controls the number of atrial impulses that can activate
ventricles. This protects ventricles against too frequent activation
during atrial tachyarrhythmias that would cause too short diastole,
too short filling and too low stroke volume.
4. AV-node can serve as a pacemaker (secondary) when the SA node
fails to function (AV-nodal rhythm is 40-55 beats/min).
LO6 – Regulation of conduction in the AV- node
Conduction velocity is called dromotropy.
Positive dromotropic intervention increases speed of
conduction; negative dromotropic interventions
decreases speed of conduction
Positive dromotropic intervention:
•sympathetic stimulation
Negative dromotropic intervention:
•parasympathetic stimulation
•ischemia
•hyperkalemia
•calcium blockers
•cardiac glycosides
•adenosine
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LO6 – Mechanisms involved in the regulation of
conduction in the AV- node
 Autonomic innervation regulates the conduction velocity mainly through the stimulation
and inhibition of the HCN- & Ca-channels and the hyperpolarization of the myocytes.
 Sympathetic stimulation speeds up the conduction velocity in the AV-node and enhance
the activity of the latent pacemakers in the AV-junction.
 Parasympathetic stimulation slows down the conduction velocity in the AV-node and
prolongs the AV-conduction time. Stronger vagal activity may cause some or all of the
impulses arriving from the atria to be blocked in the node (AV-block).
 The cardiac glycosides (e.g. digoxin), calcium channels blockers, and adenosine slow
down conduction at the AV-node.
 Mechanism of the adenosine effect: inhibition of Ca-channels and opening of adenosine
sensitive K-channels.
 Depolarization (e.g. hyperkaliemia) may inactivate calcium channels and so inhibit AP
generation and block conduction.
 Ischemia, inflammation, etc. may cause depolarisation or may destroy AV-node and AVbundle (it is only a tiny strand of tissue) and so interrupt the only electrical connection
between atria and ventricles.
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