The rhythm of the heart is normally determined by a pacemaker site

called the sinoatrial (SA) node located in the posterior wall of the
right atrium near the superior vena cava. The SA node consists of
specialized cells that undergo spontaneous generation of action
potentials at a rate of 100-110 action potentials ("beats") per minute.
This intrinsic rhythm is strongly influenced by autonomic nerves, with
the vagus nerve being dominant over sympathetic influences at rest.
This "vagal tone" brings the resting heart rate down to 60-80
beats/minute. The normal range for sinus rhythm is 60-100

beats/minute. Sinus rates below this range are termed sinus

bradycardia and sinus rates above this range are termed sinus
tachycardia.
The sinus rhythm normally controls both atrial and ventricular rhythm.
Action potentials generated by the SA node spread throughout the
atria, depolarizing this tissue and causing atrial contraction. The
impulse then travels into the ventricles via the atrioventricular node
(AV node). Specialized conduction pathways (bundle branches and
Purkinje fibers) within the ventricle rapidly conduct the wave of
depolarization throughout the ventricles to elicit ventricular
contraction. Therefore, normal cardiac rhythm is controlled by the
pacemaker activity of the SA node.
Abnormal cardiac rhythms can occur if
1.

the SA node fails to function normally (e.g., sinus

bradycardia or tachycardia)
2. impulses are not conducted from the atria to the ventricles
through the AV node (termed AV block)
3. abnormal conduction pathways are followed (e.g., accessory
pathways between atria and ventricles)
4. other pacemaker sites within the atria or ventricles (e.g., ectopic
pacemakers) trigger depolarization
General Terms:

Normal sinus rhythm - heart rhythm controlled by sinus node

at a rate of 60-100 beats/min; each P wave followed by QRS and
each QRS preceded by a P wave.
Bradycardia - a heart rate that is lower than normal.
Tachycardia - a heart rate that is higher than normal.
Paroxysmal - an arrhythmia that suddenly begins and ends.

Specific Arrhythmias:

Sinus bradycardia - low sinus rate <60 beats/min.

Sinus tachycardia - high sinus rate of 100-180 beats/min as
occurs during exercise or other conditions that lead to increased
SA nodal firing rate.
Sick sinus syndrome - a disturbance of SA nodal function that
results in a markedly variable rhythm (cycles of bradycardia and
tachycardia).
Atrial tachycardia - a series of 3 or more consecutive atrial
premature beats occurring at a frequency >100/min; usually due
to abnormal focus within the atria and paroxysmal in nature,

therefore appearance of P wave is altered in different ECG leads.

This type of rhythm includes paroxysmal atrial tachycardia (PAT).
Atrial flutter - sinus rate of 250-350 beats/min.
Atrial fibrillation - uncoordinated atrial depolarizations.
Junctional escape rhythm - SA node suppression can result in
AV node-generated rhythm of 40-60 beats/min (not preceded by
P wave).
AV nodal blocks - a conduction block within the AV node (or
occasionally in the bundle of His) that impairs impulse
conduction from the atria to the ventricles.

First-degree AV nodal block - the conduction velocity is slowed so

that the P-R interval is increased to greater than 0.2 seconds. Can be
caused by enhanced vagal tone, digitalis, beta-blockers, calcium
channel blockers, or ischemic damage.

Second-degree AV nodal block - the conduction velocity is slowed

to the point where some impulses from the atria cannot pass through
the AV node. This can result in P waves that are not followed by QRS
complexes. For example, 1 (as shown below) or 2 P waves may occur
alone before one is followed by a QRS. When the QRS follows the P
wave, the P-R interval is increased. In this type of block, the
ventricular rhythm will be less than the sinus rhythm. There are two
subtypes of second-degree AV blocks: Mobitz I and Mobitz II. In Mobitz I
(Wenkebach block), the P-R interval gradually increases over several
beats until it is sufficiently prolonged (that is, AV conduction is
sufficiently impaired) that the impulse fails to pass into the ventricles
(i.e., a P wave will not be followed by a QRS). Mobitz II occurs is when
the P-R interval is fixed in duration, but some P waves are not followed
by a QRS (as illustrated below).

Third-decree AV nodal block - conduction through the AV node is

completely blocked so that no impulses are able to be transmitted from
the atria to the ventricles. QRS complexes will still occur (escape
rhythm), but they will originate from within the AV node, bundle of His,
or other ventricular regions. Therefore, QRS complexes will not be
preceded by P waves. Furthermore, there will be complete asynchrony
between the P wave and QRS complexes. Atrial rhythm may be
completely normal, but ventricular rhythm will be greatly reduced

depending upon the location of the site generating the ventricular

impulse. Ventricular rate typically range from 30 to 40 beats/min.

Supraventricular tachycardia (SVT) - usually caused by

reentry currents within the atria or between ventricles and atria
producing high heart rates of 140-250; the QRS complex is
usually normal width, unless there are also intraventricular
conduction blocks (e.g., bundle branch block).
Ventricular premature beats (VPBs) - caused by ectopic
ventricular foci; characterized by widened QRS; often referred to
as a premature ventricular complex, or PVC.
Ventricular tachycardia (VT) - high ventricular rate caused by
aberrant ventricular automaticity (ventricular foci) or by
intraventricular reentry; can be sustained or non-sustained
(paroxysmal); usually characterized by widened QRS (>0.14 sec);
rates of 100 to 280 beats/min; life-threatening.
Ventricular flutter - very rapid ventricular depolarizations
>250/min; sine wave appearance; leads to fibrillation.
Ventricular fibrillation - uncoordinated ventricular
depolarizations; leads to death if not quickly converted to a
normal rhythm or at least a rhythm compatible with life.

The SA node displays intrinsic automaticity (spontaneous pacemaker

activity) at a rate of 100-110 action potentials ("beats") per minute.
This intrinsic rhythm is primarily influenced by autonomic nerves, with
vagal influences being dominant over sympathetic influences at rest.
This "vagal tone" reduces the resting heart rate down to 60-80
beats/min. The SA node is predominantly innervated by efferent
branches of the right vagus nerves, although some innervation from
the left vagus is often observed. Experimental denervation of the right
vagus to the heart leads to an abrupt increase in SA nodal firing rate if
the resting heart rate is below 100 beats/min. A similar response is
noted when a drug such as atropine is administered. This drug blocks
vagal transmission at the SA node by antagonizing the muscarinic
receptors that bind to acetylcholine, which is the neurotransmitter
released by the vagus nerve.

Parasympathetic (vagal) activation, which releases acetylcholine (ACh)

onto the SA node, decreases pacemaker rate by increasing gK+ and
decreasing slow inward gCa++ and gNa+; the pacemaker current (If) is
suppressed. These ionic conductance changes decrease the slope of
phase 4 of the action potential, thereby increasing the time required to
reach threshold. Vagal activity also hyperpolarizes the pacemaker cell
during Phase 4, which results in a longer time to reach threshold
voltage.
The rate of SA nodal firing can be altered by:
1.
changes in autonomic nerve activity (sympathetic and
vagal)
To increase heart rate, the autonomic nervous system increases
sympathetic outflow to the SA node, with concurrent inhibition of
vagal tone. Inhibition of vagal tone is necessary for the
sympathetic nerves to increase heart rate because vagal
influences inhibit the action of sympathetic nerve activity.
Sympathetic activation, which releases norepinephrine (NE),
increases pacemaker rate by decreasing gK+ and increasing slow
inward gCa++ and gNa+; the pacemaker current (If) is enhanced.
These changes increase the slope of phase 4 so that the
pacemaker potential more rapidly reaches the threshold for
action potential generation.
2. circulating hormones
Pacemaker activity is also altered by hormones. For example,
hyperthyroidism induces tachycardia and hypothyroidism
induces bradycardia. Circulating epinephrine causes tachycardia
by a mechanism similar to norepinephrine released by
sympathetic nerves.
3. serum ion concentrations

Changes in the serum concentration of ions, particularly

potassium, can cause changes in SA nodal firing rate.
Hyperkalemia induces bradycardia or can even stop SA nodal
firing. Hypokalemia increases the rate of phase 4 depolarization
and causes tachycardia. It apparently does this by decreasing gK
during phase 4.
4. cellular hypoxia
Cellular hypoxia (usually due to ischemia) depolarizes the
membrane potential causing bradycardia; severe hypoxia
completely stops pacemaker activity.
5. drugs
Various drugs used as antiarrhythmics also affect SA nodal
rhythm. Calcium-channel blockers, for example, cause
bradycardia by inhibiting the slow inward Ca++ currents during
phase 4 and phase 0. Drugs affecting autonomic control or
autonomic receptors (e.g., beta-blockers, muscarinic antagonists)
directly or indirectly alter pacemaker activity. Digitalis causes
bradycardia by increasing parasympathetic (vagal) activity on
the SA node; however, at toxic concentrations, digitalis increases
automaticity and therefore can cause tachyarrhythmias. This
toxic effect is related to the inhibitory effects of digitalis on the
membrane Na+/K+-ATPase, which leads to cellular depolarization,
increased intracellular calcium, and changes in ion
conductances.
Pacemaker activity is influenced dramatically by age. The maximal
heart rate that can be achieved in an individual is estimated by
Maximal Heart Rate = 220 beats/min age in years
Therefore a 20-year-old person will have a maximal heart rate of about
200 beats/min, and this will decrease to about 170 beats/min when the
person is 50 years of age. This maximal heart rate is genetically
determined and cannot be modified by exercise training or by external
factors.
Cells within the sinoatrial (SA) node are the primary pacemaker site
within the heart. These cells are characterized as having no true
resting potential, but instead generate regular, spontaneous action
potentials. Unlike non-pacemaker action potentials in the heart, and
most other cells that elicit action potentials (e.g., nerve cells, muscle
cells), the depolarizing current is carried into the cell primarily by

relatively slow Ca++ currents instead of by fast Na+ currents. There are,
in fact, no fast Na+ channels and currents operating in SA nodal cells.
This results in a slower action potentials in terms of how rapidly they
depolarize. Therefore, these pacemaker action potentials are
sometimes referred to as "slow response" action potentials.

SA nodal action potentials are divided into three phases. Phase 4 is

the spontaneous depolarization (pacemaker potential) that triggers the
action potential once the membrane potential reaches threshold
between -40 and -30 mV). Phase 0 is the depolarization phase of the
action potential. This is followed by phase 3 repolarization. Once the
cell is completely repolarized at about -60 mV, the cycle is
spontaneously repeated.
The changes in membrane potential during the different phases are
brought about by changes in the movement of ions (principally Ca++
and K+, and to a lesser extent Na+) across the membrane through ion
channels that open and close at different times during the action
potential. When a channel is opened, there is increased electrical
conductance (g) of specific ions through that ion channel. Closure of
ion channels causes ion conductance to decrease. As ions flow through
open channels, they generate electrical currents (i or I) that change the
membrane potential.
In the SA node, three ions are particularly important in
generating the pacemaker action potential. The role of these ions in
the different action potential phases are illustrated in the above figure
and described below:

At the end of repolarization, when the membrane potential is

very negative (about -60 mV), ion channels open that conduct
slow, inward (depolarizing) Na+ currents. These currents are

called "funny" currents and abbreviated as "If". These

depolarizing currents cause the membrane potential to begin to
spontaneously depolarize, thereby initiating Phase 4. As the
membrane potential reaches about -50 mV, another type of
channel opens. This channel is called transient or T-type Ca++
channel. As Ca++ enters the cell through these channels down
its electrochemical gradient, the inward directed Ca++ currents
further depolarize the cell. As the membrane continues to
depolarize to about -40 mV, a second Ca++ channel opens. These
are the so-called long-lasting, or L-type Ca++ channels.
Opening of these channels causes more Ca++ to enter the cell
and to further depolarize the cell until an action potential
threshold is reached (usually between -40 and -30 mV). During
Phase 4 there is also a slow decline in the outward movement of
K+ as the K+ channels responsible for Phase 3 continue to close.
This fall in K+ conductance (gK+) contributes to the depolarizing
pacemaker potential.
Phase 0 depolarization is primarily caused by increased Ca++
conductance (gCa++) through the L-type Ca++ channels that
began to open toward the end of Phase 4. The "funny" currents,
and Ca++ currents through the T-type Ca++ channels, decline
during this phase as their respective channels close. Because the
movement of Ca++ through these channels into the cell is not
rapid, the rate of depolarization (slope of Phase 0) is much
slower than found in other cardiac cells (e.g., Purkinje cells).
Repolarization occurs (Phase 3) as K+ channels open (increased
gK+) thereby increasing the outward directed, hyperpolarizing K+
currents. At the same time, the L-type Ca++ channels become
inactivated and close, which decreases gCa++ and the inward
depolarizing Ca++ currents.

During depolarization, the membrane potential (Em) moves toward the

equilibrium potential for Ca++, which is about +134 mV. During
repolarization, gCa++ (relative Ca++ conductance) decreases and gK+
(relative K+ conductance) increases, which brings Em closer toward the
equilibrium potential for K+, which is about -96 mV). Therefore, the
action potential in SA nodal cells is primarily dependent upon changes
in Ca++ and K+ conductances as summarized below:
Em = g'K+ (-96 mV) + g'Ca++ (+134 mV)
Although pacemaker activity is spontaneously generated by SA nodal
cells, the rate of this activity can be modified significantly by external
factors such as by autonomic nerves, hormones, drugs, ions, and
ischemia/hypoxia.

It is important to note that action potentials described for SA nodal

cells are very similar to those found in the atrioventrcular (AV) node.
Therefore, action potentials in the AV node, like the SA node, are
determined primarily by changes in slow inward Ca++ and K+ currents,
and do not involve fast Na+ currents. AV nodal action potentials also
have intrinsic pacemaker activity produced by the same ion currents as
described above for SA nodal c
Atrial myocytes, ventricular myocytes and Purkinje cells are examples
of non-pacemaker action potentials in the heart. Because these action
potentials undergo very rapid depolarization, they are sometimes
referred to as "fast response" action potentials.
Unlike pacemaker cells found in nodal tissue within the heart, nonpacemaker cells have a true resting membrane potential (phase 4)
that remains near the equilibrium potential for K+ (EK). The resting
membrane potential is very negative during phase 4 (about -90 mV)
because potassium channels are open (K+ conductance [gK+] and K+
currents [IK] are high). As shown in the figure, phase 4 is associated
with K+ currents, in which positive potassium ions are leaving the cell
and thereby making the membrane potential more negative inside. At
the same time, fast sodium channels and (L-type) slow calcium
channels are closed.
When these cells are rapidly depolarized to a threshold voltage of
about -70 mV (e.g., by an action potential in an adjacent cell), there is
a rapid depolarization (phase 0) that is caused by a transient increase
in fast Na+-channel conductance (gNa+) through fast sodium channels.
This increases the inward directed, depolarizing Na+ currents (INa) that
are responsible for the generation of these "fast-response" action
potentials (see above figure). At the same time sodium channels open,
gK+ and outward directed K+ currents fall as potassium channels close.
These two conductance changes move the membrane potential away
from EK (which is negative) and closer toward the equilibrium potential
for sodium (ENa), which is positive.
Phase 1 represents an initial repolarization that is caused by the
opening of a special type of transient outward K+ channel (Kto), which
causes a short-lived, hyperpolarizing outward K+ current (IKto). However,
because of the large increase in slow inward gCa++ occurring at the
same time and the transient nature of IKto, the repolarization is delayed
and there is a plateau phase in the action potential (phase 2). This
inward calcium movement is through long-lasting (L-type) calcium
channels that open up when the membrane potential depolarizes to
about -40 mV. This plateau phase prolongs the action potential

duration and distinguishes cardiac action potentials from the much

shorter action potentials found in nerves and skeletal muscle.
Repolarization (phase 3) occurs when gK+ (and therefore IK) increases,
along with the inactivation of Ca++ channels (decreased gCa++).

Therefore, the action potential in non-pacemaker cells is primarily

determined by relative changes in fast Na+, slow Ca++ and K+
conductances and currents. As described under the discussion on
membrane potentials and summarized in the following relationship and
in the figure to the right, the membrane potential (Em) is determined
by the relative conductances of the major ions distributed across the
cell membrane. When g'K+ is high and g'Na+ and g'Ca++ are low
(phases 3 and 4), the membrane potential will be more negative. When
g'K+ is low and g'Na+ and/or g'Ca++ are high, the membrane potential
will be more positive (phases 0, 1 and 2).
Em = g'K+ (96 mV) + g'Na+ (+50 mV) + g'Ca++ (+134 mV)
These fast-response action potentials in non-nodal tissue are altered by
antiarrhythmic drugs that block specific ion channels. Sodium-channel
blockers such as quinidine inactivate fast-sodium channels and reduce
the rate of depolarization (decrease the slope of phase 0). Calciumchannel blockers such as verapamil and diltiazem affect the plateau
phase (phase 2) of the action potential. Potassium-channel blockers
delay repolarization (phase 3) by blocking the potassium channels that
are responsible for this phase.
Effective Refractory Period

Once an action potential is initiated, there is a period of time

comprising phases 0, 1, 2, and part of phase 3 that a new action
potential cannot be initiated. This is termed the effective refractory
period (ERP) or the absolute refractory period (ARP) of the cell.
During the ERP, stimulation of the cell by an adjacent cell undergoing
depolarization does not produce new, propagated action potentials.
The ERP acts as a protective mechanism in the heart by preventing
multiple, compounded action potentials from occurring (i.e., it limits
the frequency of depolarization and therefore heart rate). This is
important because at very high heart rates, the heart would be unable
to adequately fill with blood and therefore ventricular ejection would be
reduced.
Many antiarrhythmic drugs alter the ERP, thereby altering cellular
excitability. For example, drugs that block potassium channels (e.g.,
amiodarone, a Class III antiarrhythmic) delays phase 3 repolarization
and increases the ERP. Drugs that increase the ERP can be particularly
effective in abolishing reentry currents that lead to tachyarrhythmias.
Transformation of non-pacemaker into pacemaker cells
It is important to note that non-pacemaker action potentials can
change into pacemaker cells under certain conditions. For example, if a
cell becomes hypoxic, the membrane depolarizes, which closes fast
Na+ channels. At a membrane potential of about 50 mV, all the fast
Na+ channels are inactivated. When this occurs, action potentials can
still be elicited; however, the inward current are carried by Ca++ (slow
inward channels) exclusively. These action potentials resemble those
found in pacemaker cells located in the SA node, and can sometimes
display spontaneous depolarization and automaticity. This mechanism
may serve as the electrophysiological mechanism behind certain types
of ectopic beats and arrhythmias, particularly in ischemic heart
disease and following myocardial infarction.

Determining Heart Rate from the Electrocardiogram

The term "heart rate" normally refers to the rate of
ventricular contractions. However, because there are circumstances in
which the atrial and ventricular rates differ (e.g., second and third
degree AV block), it is important to be able to determine both atrial
and ventricular rates. This is easily done by examining an ECG rhythm
strip, which is usually taken from Lead II. In the example below, there
are four numbered R waves, each of which is preceded by a P wave.
Therefore, the atrial and ventricular rates will be the same because
there is a one-to-one correspondence. Atrial rate can be determined by
measuring the time intervals between P waves (P-P intervals).
Ventricular rate can be determined by measuring the time intervals
between the QRS complexes, which is done by looking at the R-R
intervals.

There are different short-cut methods that can be used to calculate

rate, all of which assume a recording speed of 25 mm/sec. One method
is to divide 1500 by the number of small squares between two R
waves. For example, the rate between beats 1 and 2 in the above
tracing is 1500/22, which equals 68 beats/min. Alternatively, one can
divide 300 by the number of large squares (red boxes in this diagram),
which is 300/4.4 (68 beats/min). Another method, which gives a rough
approximation, is the "count off" method. Simply count the number of
large squares between R waves with the following rates: 300 - 150 100 - 75 - 60. For example, if there are three large boxes between R
waves, then the rate is 100 beats/min. One must extrapolate, however,
between boxes. Atrial rate can be determined like the ventricular rate,
but using the P waves. Remember, if the heart in in sinus rhythm and
there is a one-to-one correspondence between P waves and QRS
completes, then the atrial rate will be the same as ventricular rate.
In the above examples, the ventricular rate was determined based on
the interval between the first two beats. However, it is obvious that the
rate would have been faster had it been calculated using beats 2 and 3
(104 beats/min) because because of a premature atrial beat, and

slower if it had been calculated between beats 3 and 4 (52 beats/min).

This illustrates an important point when calculating rate between any
given pair of beats. If the rhythm is not steady, it is important to
determine a time-averaged rate over a longer interval (e.g., over ten
seconds or longer). For example, because the recording time scale is
25 mm/sec, if there are 12.5 beats in 10 seconds, the rate will be 75
beats/min.
Electrocardiogram Standard Limb Leads (Bipolar)

Bipolar recordings utilize standard limb lead configurations depicted at

the right. By convention, lead I has the positive electrode on the left
arm, and the negative electrode on the right arm, and therefore
measures the potential difference between the two arms. In this and
the other two limb leads, an electrode on the right leg serves as a
reference electrode for recording purposes. In the lead II configuration,
the positive electrode is on the left leg and the negative electrode is on
the right arm. Lead III has the positive electrode on the left leg and the
negative electrode on the left arm. These three bipolar limb leads
roughly form an equilateral triangle (with the heart at the center) that
is called Einthoven's triangle in honor of Willem Einthoven who
developed the electrocardiogram in 1901. Whether the limb leads are
attached to the end of the limb (wrists and ankles) or at the origin of
the limb (shoulder or upper thigh) makes no difference in the recording
because the limb can simply be viewed as a long wire conductor
originating from a point on the trunk of the body.
Based upon universally accepted ECG rules, a wave a depolarization
heading toward the left arm gives a positive deflection in lead I
because the positive electrode is on the left arm. Maximal positive
ECG deflection occurs in lead I when a wave of depolarization travels
parallel to the axis between the right and left arms. If a wave of
depolarization heads away from the left arm, the deflection is
negative. Also by these rules, a wave of repolarization moving away
from the left arm is recorded as a positive deflection. Similar

statements can be made for leads II and III in which the positive
electrode is located on the left leg. For example, a wave of
depolarization traveling toward the left leg produces a positive
deflection in both leads II and III because the positive electrode for
both leads is on the left leg. A maximal positive deflection is recorded
in lead II when the depolarization wave travels parallel to the axis
between the right arm and left leg. Similarly, a maximal positive
deflection is obtained in lead III when the depolarization wave travels
parallel to the axis between the left arm and left leg.

If the three limbs of Einthoven's triangle (assumed to be equilateral)

are broken apart, collapsed, and superimposed over the heart, then the
positive electrode for lead I is said to be at zero degrees relative to the
heart (along the horizontal axis) (see figure at right). Similarly, the
positive electrode for lead II will be +60 relative to the heart, and the
positive electrode for lead III will be +120 relative to the heart as
shown to the right. This new construction of the electrical axis is called
the axial reference system. With this system, a wave of
depolarization traveling at +60 produces the greatest positive
deflection in lead II. A wave of depolarization oriented +90 relative to
the heart produces equally positive deflections in both lead II and III.
In this latter example, lead I shows no net deflection because the wave
of depolarization is heading perpendicular to the 0, or lead I, axis (see
ECG rules).
For a heart with a normal ECG and a mean electrical axis of +60, the
standard limb leads will appear as follows:

The electrocardiogram uses electrodes on the surface of the body to

measure the electrical activity of the heart. It is possible to place
electrodes on the body surface and measure cardiac potentials
because the body acts as a conductor of the electrical currents
generated by the heart. What do these electrodes actually measure?

If a piece of living ventricular muscle is placed in a bath containing a

salt solution to conduct electrical currents, and electrodes are placed in
the bath on either side of the muscle, no potential difference would be
recorded between the two electrodes when the muscle is in its
polarized, resting state (top panel of figure at right). The reason for
this is that the outside of the cells is positive relative to the inside
because the resting membrane potential is be about -90 mV; therefore,
no currents will flow along the surface of the muscle and through the
bath. If the left side of the muscle is stimulated electrically to induce
self-propagating action potentials, a wave of depolarization would
sweep across the muscle from left-to-right (lower panel). Midway
through this depolarization process, cells on the left (depolarized cells)
would be negative on the outside relative to the inside, while non-

depolarized cells on the right of the muscle would still be polarized

(positive on the outside). There would now exist a potential difference
between the positive and negative electrodes. By convention, a wave
of depolarization heading toward the positive electrode is recorded as
a positive voltage (upward deflection in the recording). After the wave
of depolarization sweeps across the entire muscle mass, all the cells on
the outside are negative, and once again, no potential difference would
exist between the two electrodes.

The entire process of depolarization and repolarization is depicted in

the animated model to the right, which is representative of the
electrical events that occur in the atria. In the resting, polarized state,
no potential difference is measured between the positive and negative
electrodes (i.e., isoelectric - flat red line). When the left side of the
tissue becomes depolarized (representing firing of the SA node), a
wave of depolarization begins to spread across the atria. During this
time, some of the muscle mass temporarily remains positive on the
outside (polarized) and while some is negative (depolarized); thus,
there is a separation of charges which causes a potential difference
between the two electrodes. Because the wave of depolarization is
moving toward the positive electrode, by convention, a positive
voltage (upward deflection) is recorded. The voltage reaches its
maximal positive value when half the tissue is depolarized. Once the
entire atrial mass is depolarized (all cells negative on outside), there is
no longer be a potential difference and the voltage is zero just as it was
in the polarized state. When repolarization occurs, starting first with
the left side ( SA nodal region) then moving across the atria, there will
once again be both positive and negative charges on the surface of the
atria, but this time, the negative charges will be closest to the positive
electrode. The wave of repolarization sweeping across the atria away
from the negative electrode and toward the positive electrode causes,
by convention, a negative voltage (downward deflection) to occur.
Finally, when all of the cells are repolarized, the measured voltage
difference will once again be zero until another wave of depolarization
occurs.

A similar process occurs within the ventricles with one major

difference: repolarization normally occurs in a direction opposite to
depolarization. In other words, the last cells in the ventricle to
depolarize are the first to repolarize. This results in a positive
recording as the ventricles repolarize as shown in the animated model
to the right.
Several important observations and rules emerge from these volume
conductor considerations:
1. A wave of depolarization traveling toward a positive
electrode results in a positive deflection in the ECG trace.
2. A wave of depolarization traveling away from a positive
electrode results in a negative deflection.
3. A wave of repolarization traveling toward a positive
electrode results in a negative deflection.
4. A wave of repolarization traveling away from a positive
electrode results in a positive deflection.
5. A wave of depolarization or repolarization traveling
perpendicular to an electrode axis results in a biphasic
deflection of equal positive and negative voltages (i.e.,
no net deflection).
6. The instantaneous amplitude of the measured potentials
depends upon the orientation of the positive electrode
relative to the mean electrical vector.
7. The voltage amplitude is directly related to the mass of
tissue undergoing depolarization or repolarization.
The first four rules are derived from the volume conductor model
described above. The fifth rule is also based on volume conductor
principles and could be modeled by placing the positive and negative
electrodes midway on the top and bottom surfaces of the tissue
instead of on the ends. In this case, the positive electrode would first
measure a positive voltage as the wave of depolarization transverse
the tissue from the left edge to the midpoint (toward the electrode),

and then the electrode would measure a negative voltage as the wave
moved away from the electrode to the right edge. The sixth rule takes
into consideration that at any given point in time during depolarization
in the atria or ventricles there are many separate waves of
depolarization traveling in different directions relative to the positive
electrode. The recording by the electrode reflects the average,
instantaneous direction and magnitude (i.e., mean electrical vector) for
all of the individual depolarization waves. The seventh rule simply
states that the amplitude of the wave recorded by the ECG is directly
related to the mass of the muscle undergoing depolarization or
repolarization. For example, when the mass of the left ventricle is
increased by hypertrophy, the voltage amplitude of the QRS complex,
which represents ventricular depolarization, is increased in certain
leads.
Electrocardiogram Augmented Limb Leads (Unipolar)

In addition to the three bipolar limb leads described above, there are
three augmented unipolar limb leads. These are termed unipolar leads
because there is a single positive electrode that is referenced against a
combination of the other limb electrodes. The positive electrodes for
these augmented leads are located on the left arm (aVL), the right arm
(aVR), and the left leg (aVF). In practice, these are the same electrodes
used for leads I, II and III. (The ECG machine does the actual switching

and rearranging of the electrode designations). The three augmented

leads, along with the three standard bipolar limb leads, are depicted as
shown to the right using the axial reference system. The aVL lead is at
-30 relative to the lead I axis; aVR is at -150 and aVF is at +90. It is
very important to learn which lead is associated with each axis.
The three augmented unipolar leads, coupled with the three bipolar
leads, constitute the six limb leads of the ECG. These leads record
electrical activity along a single plane, termed the frontal plane relative
to the heart. Using the axial reference system and these six leads, it is
simple to define the direction of an electrical vector at any given
instant in time. If a wave of depolarization is spreading from right-toleft along the 0 axis, then lead I will show the greatest positive
amplitude. If the direction of the electrical vector for depolarization is
directed downwards (+90), then aVF will show the greatest positive
deflection. If a wave of depolarization is moving from left-to-right at
+150, then aVL will show the greatest negative deflection according to
the rules for ECG interpretation.
For a heart with a normal ECG and mean electrical axis of +60, the
augmented leads will appear as shown below:

Electrocardiogram Chest Leads (Unipolar)

In addition to the three standard limb leads and the three augmented
limb leads that view the electrical activity of the heart from the frontal
plane, there are six precordial, unipolar chest leads. This configuration
places six positive electrodes on the surface of the chest over different
regions of the heart in order to record electrical activity in a plane
perpendicular to the frontal plane (see figure at right). These six leads
are named V1 - V6. The rules of interpretation are the same as for the
limb leads. For example, a wave of depolarization traveling toward a
particular electrode on the chest surface will elicit a positive
deflection.
The chest leads overlie the following ventricular regions:
Lead
Ventricular
s
Region
V1-V2 anteroseptal
V3-V4 anteroapical
V5-V6 anterolateral
This placement of chest leads produces the following normal ECG
tracings:

Because initial ventricular depolarization is from left to right across the

septum, there is an initial R-wave in V1 followed by an S-wave as the
anterior and lateral walls of the left ventricle depolarize. Leads V5 and
V6 show a large net positive QRS because these leads overlie the
anterolateral wall of the left ventricle, which has a large muscle mass
undergoing depolarization. Tracings from leads V5 and V6 are almost
opposite in polarity from V1 because they are viewing opposite sides of
the heart. Leads V2-V4 are intermediate owing to their electrode
placement.
In summary, the chest leads provide a different view of the electrical
activity within the heart. Therefore, the waveform recorded is different
for each lead compared to the limb leads. To understand how cardiac
electrical currents actually generate and ECG tracing and why the
different leads display that electrical activity differently, it is necessary
to understand volume conductor principles and vectors.
Ventricular Depolarization and the Mean Electrical Axis
Sequence of Ventricular Depolarization

The mean electrical axis is the average of all the instantaneous mean
electrical vectors occurring sequentially during depolarization of the
ventricles. The figure to the right depicts the sequence of
depolarization within the ventricles. The septum and free left and right
ventricular walls are shown. In this model, each of the four vectors is
depicted as originating from the top of the interventricular septum just
below the AV node. The electrode placement represents lead II.
During ventricular activation, impulses are first conducted down the
left and right bundle branches on either side the septum. This causes
the septum to depolarize from left-to-right as depicted by vector 1
(Panel A). This vector is heading slightly away from the positive
electrode (to the right of a line perpendicular to the lead axis) and
therefore will record a small negative deflection (Q wave of the QRS).
About 20 milliseconds later, the mean electrical vector points
downward toward the apex (vector 2), and is heading toward the
positive electrode (Panel B). This will produce a very tall positive
deflection (R wave of the QRS). After another 20 milliseconds later, the
mean vector is pointing toward the left arm and anterior chest as the
free wall of the ventricle depolarizes from the endocardial to the
epicardial surface (vector 3, Panel C). This vector will record a small
positive voltage in lead II. Finally, the last regions to depolarize will
result in vector 4 (Panel D), which will cause a slight negative
deflection (S wave) of the QRS.

The shape of the QRS complex is different for each of the limb leads
because each of the leads will "see" the sequence of depolarization
vectors from a different perspective (see axial reference system). The
animated figure to the right shows how the QRS complex appears for
leads aVF and aVL. The positive electrodes for these two leads are at
+90 and -30, respectively. In this illustration, the mean electrical
axis (see below) is about +45. Note that aVF shows a large net
positive QRS. There is no Q wave because septal depolarization is not
directed away from the lead (see ECG rules). The R wave is very
positive because early ventricular depolarization is largely directed
toward this lead. The S wave is also present because the terminal
depolarization of the upper wall of the left ventricle is directed away
from aVF. In contrast, aVL shows an initial Q wave (septal depolarization
is directed away from the lead) followed by a moderately positive R
wave.
The Mean Electrical Axis

In the above illustration, the mean electrical axis will be the sum of
all of the mean electrical vectors. The mean electrical axis is depicted
by the red arrow in the figure above and in the figure to the right,
which is the same figure superimposed upon the axial reference

system. In this example, the mean electrical axis is approximately

+30. The mean electrical axis for the heart normally lies between -30
and +90. (Some textbooks say the normal range is 0 to +90.) Less
than -30 (or less than 0) is termed a left axis deviation and greater
than +90 is termed a right axis deviation. Axis deviations can be
caused by increased cardiac muscle mass (e.g., left ventricular
hypertrophy), changes in the sequence of ventricular activation (e.g.,
conduction defects), or because of ventricular regions being incapable
of being activated (e.g., infarcted tissue).
The mean electrical axis corresponds to the axis that is perpendicular
to the lead axis that has the smallest net QRS amplitude (net
amplitude = positive minus negative deflection voltages of QRS
complex). In the above figure, lead III would have the smallest net
amplitude (the ECG would be biphasic with equal positive and negative
deflections). The mean electrical axis, therefore, is perpendicular to
lead III, which is 120 minus 90, or approximately +30 in this
example. Leads I and II will have equally positive QRS deflections.
Lead aVR would have the greatest negative deflection.
To determine the mean electrical axis from the ECG, find the lead axis
that has a biphasic (equally positive and negative QRS deflections i.e., no net deflection), then find the lead axis that is perpendicular
(90) to the biphasic lead and that has a positive net deflection. In the
six limb leads in the example below, aVL is biphasic. The positive
perpendicular axis to aVL is +60. Therefore, the mean electrical axis is
+60, which is normal.

Membrane Potentials
Note: An 18 minute mini-lecture on this topic can be viewed
at the end of this page.
If a voltmeter is attached to the two terminals of a battery, a voltage
difference will be measured across the two terminals. Likewise, if a
voltmeter is used to measure voltage across the cell membrane (inside
versus outside) of a cardiomyocyte, it will be found that the inside of
the cell has a negative voltage (measured in millivolts; mV) with
respect to the outside of the cell (which is referenced as 0 mV). Under
resting conditions, this is called the resting membrane potential.
With appropriate stimulation of the cell, this negative voltage inside
the cell (negative membrane potential) may transiently become
positive owing to the generation of an action potential. Membrane
potentials result from a separation of positive and negative charges
(ions) across the membrane, similar to the plates within a battery that
separate positive and negative charges.
Membrane potentials in cells are determined primarily by three factors:
1) the concentration of ions on the inside and outside of the cell; 2) the
permeability of the cell membrane to those ions (i.e., ion conductance)
through specific ion channels; and 3) by the activity of electrogenic

pumps (e.g., Na+/K+-ATPase and Ca++ transport pumps) that maintain

the ion concentrations across the membrane.

Cardiac cells, like all living cells, have different concentrations of ions
across the cell membrane, the most important of which are Na+, K+, Cl-,
and Ca++ (see figure to right). There are also negatively charged
proteins within the cell to which the cell membrane is impermeable. In
a cardiac cell, the concentration of K+ is high inside the cell and low
outside. Therefore, there is a chemical gradient for K+ to diffuse out of
the cell. The opposite situation is found for Na+ and Ca++ where their
chemical gradients (high outside, low inside concentrations) favor an
inward diffusion.
Potassium ion
To understand how a membrane potential is generated, first consider a
hypothetical cell in which K+ is the only ion across the membrane other
than the large negatively charged proteins inside of the cell. Because
the cell has potassium channels through which K+ can move in and
out of the cell, K+ diffuses down its chemical gradient (out of the cell)
because its concentration is much higher inside the cell than outside.
As K+ (a positively charged ion) diffuses out of the cell, it leaves behind
negatively charged proteins. This leads to a separation of charges
across the membrane and therefore a potential difference across the
membrane. Experimentally it is possible to prevent the K+ from
diffusing out of the cell. This can be achieved by applying a negative
charge to the inside of the cell that prevents the positively charged K+
from leaving the cell. The negative charge across the membrane that
would be necessary to oppose the movement of K+ down its
concentration gradient is termed the equilibrium potential for K+
(EK; Nernst potential). The Nernst potential for K+ can be calculated
as follows:

(where [K+]i = 150 mM and [K+]o = 4 mM; and z=1 because K+ is

monovalent)
The EK represents the electrical potential necessary to keep K+ from
diffusing out of the cell, down its chemical gradient. If the outside K+
concentration were increased from 4 to 40 mM, then the chemical
gradient driving K+ out of the cell would be reduced, and therefore the
membrane potential required to maintain electrochemical equilibrium
(EK) would be less negative according to the Nernst relationship. In this
example, the EK becomes -35 mV when the outside K+ concentration is
40 mM. In other words, when K+ is elevated 10-fold outside of the cell,
the chemical gradient driving K+ out of the cell is reduced and
therefore a less negative voltage is required to keep K+ from diffusing
out of the cell.
The resting potential for a ventricular myocyte is about -90 mV, which
is near the equilibrium potential for K+ when extracellular K+
concentration is 4 mM. Since the equilibrium potential for K+ is -96 mV
and the resting membrane potential is -90 mV, there is a net
electrochemical driving force (difference between membrane potential
and equilibrium potential) of 6 mV acting on the K+. The membrane
potential is more positive than the equilibrium potential, therefore the
net driving force is outward due to K+ having a positive charge.
Because the resting cell has a finite permeability to K+ and the
presence of a small net outward driving force acting upon K+, there is
a slow outward leak of K+ from the cell. If K+ continued to leak out of
the cell, its chemical gradient would be lost over time; however, a
Na+/K+-ATPase pump brings the K+ back into the cell and thereby
maintains the K+ chemical gradient.
Sodium and calcium ions
Because the Na+ concentration is higher outside the cell, this ion
diffuses down its chemical gradient into the cell. Experimentally, this
inward diffusion of Na+ can be prevented by applying a positive charge
to the inside of the cell. When this positive change counterbalances the
chemical diffusion force driving Na+ into the cell, there will be no net
movement of Na+ into the cell, and Na+ will therefore be in
electrochemical equilibrium. The membrane potential required to
produce this electrochemical equilibrium is called the equilibrium
potential for Na+(ENa) and is calculated by:

(where [Na+]i = 20 mM and [Na+]o = 145 mM; and z=1 because Na+ is
monvalent)
The positive ENa means that in order to balance the inward directed
chemical gradient for Na+, the cell interior needs to be +52 mV to
prevent Na+ from diffusing into the cell. At a resting membrane
potential of -90 mV, there is not only a large chemical driving force, but
also a large electrical driving force acting upon external Na+ to cause it
to diffuse into the cell. The difference between the membrane potential
and the equilibrium potential (-142 mV) represents the net
electrochemical force driving Na+ into the cell at resting membrane
potential. At rest, however, the permeability of the membrane to Na+ is
very low so that only a small amount Na+ leaks into the cell. During an
action potential, the cell membrane become more permeable to Na+,
which increases sodium entry into the cell through sodium
channels. At the peak of the action potential in a cardiac cell (e.g.,
ventricular myocyte), the membrane potential is approximately +20
mV. Therefore, while the resting potential is far removed from the ENa,
the peak of the action potential approaches ENa. Because a small
amount of Na+ enters the cell at rest, and a relatively large amount of
Na+ enters during action potentials, a Na+/K+-ATPase pump is required
to transport Na+ out of the cell (in exchange for K+) in order to maintain
the chemical gradient for Na+.
Similar to Na+, there is a large Ca++ concentration difference across the
cell membrane. Therefore, Ca++ diffuses into the cell through calcium
channels. Applying the Nernst equation to external and internal
calcium concentrations of 2.5 mM and 0.0001 mM, respectively, results
in an equilibrium potential of +134 mV as shown below.

This value also includes that the fact that Ca++ is a divalent instead of a
monovalent cation; therefore, the -61 constant in the above equation is
divided by 2 because z = 2 (z = number of charges). Because the
equilibrium potential is much more positive than the resting membrane
potential, there is a net electrochemical force trying to drive Ca++ into
the cell, which occurs when the calcium channels are open.

The above discussion shows how changes in the concentration of

individual ions across the membrane can alter the membrane
potential. However, to fully understand how multiple ions affect the
membrane potential, and ultimately how the membrane potential
changes during action potentials, it is necessary to learn how changes
in membrane ion permeability, that is, changes in ion conductance,
affect the membrane potential. Furthermore, electrogenic ion pumps
such as the Na+/K+-ATPase pump contribute to the membrane potential
as they transport ions across the membrane to maintain the ion
concentrations across the membrane.
The following is a mini-lecture on cardiac membrane potentials (18.2
minutes in length):