Chapter 2

THE ELECTRICAL ACTIVITY OF THE HEART

Learning Objectives

After reading this chapter you should be able to:

1. Explain the ionic basis of the cardiac action potential recorded from myocytes and
from the SA node.
2. Understand the relationship between the electrophysiological and mechanical events
in the heart.
3. Explain how the wave of depolarization spreads throughout the heart.
4. Explain the significance of the delay at the AV node.
5. Explain why the SA node is the pacemaker of the heart.
6. Describe how the parasympathetic nervous system decreases heart rate.
7. Describe how the sympathetic nervous system increases heart rate.

Introduction

Skeletal muscles contract only in response to activity in motor nerves. In contrast, the heart
can initiate its own contraction because it possesses an electrical system (of modified
myocytes) consisting of:

Sinoatrial (SA) node

Atrioventricular (AV) node

Bundle of His

Purkinje fibres

Figure 1 Diagram showing the conducting

system of the heart.
(Rhoades and Bell Medical Physiology)

1
Action potentials are generated spontaneously in the SA node (located in the right atrium).
They travel along internodal pathways to the atrial myocardium, through the AV node and
then along the Bundle of His and Purkinje fibres to trigger action potentials in ventricular
myocardial cells which then contract to perform the contractile work of the heart.

This chapter deals with cardiac electrophysiology:

How action potentials are generated in the SA node

The different phases of the cardiac action potential

How they are conducted along the electrical system to trigger action potentials
in myocardial cells

How the autonomic nervous system modulates heart rate and excitability.

The different phases of the myocardial action potential will be described in detail because in
pharmacology you will be learning about anti-arrhythmic drugs which act by blocking
various ion channels thus affecting the cardiac action potential and the overall excitability of
the heart.

Cardiac action potentials, like nerve and muscle action potentials are due to the sequential
opening and closing of various ion channels. Remember that ion channels can be opened in
response to a transmitter binding to a receptor (ligand-gated channels) or to changes in
membrane potential (voltage-gated channels). Irrespective of what kind of channel it is, once
a particular ion channel is open ions will flow through that channel, carrying an electrical
current, in the direction dictated by the concentration gradient of that particular ion. Should a
Na channel be opened this results in an inward Na current (iNa). Opening a K channels
creates an outward iK. For each ion, there are several channels through which it can flow. The
channels are denoted sometimes by the subscript added to i - which denotes the ionic
current.
Cardiac action potentials are more complex than neuronal and skeletal muscle action
potentials: they last 300 400 ms and involve the opening of more types of ion channels
including Ca channels.

We will start off by considering action potentials in ventricular myocardial cells. These form
part of the contractile myocardium and in healthy individuals, do not generate action
potentials spontaneously but only when they are triggered to do so by an action potential in a
neighbouring myocyte.

2
Ventricular Myocardial Muscle Cell (Myocytes)
Resting Membrane Potential: ~ - 85 mV

How is this RMP generated?

The RMP arises because (just like in neurons and muscles):-

1. [K+]i > [K+]o

2. Myocardial membrane is very permeable to K+ (gK is high) such that K+ flows

out through inward rectifier channels (iK1).

The Potassium Equilibrium Potential (EK): ~ -95 mV

This means that when the membrane potential of the myocyte is -95 mV there is no net flow
of K+ across the membrane since the amount of K+ diffusing out down its concentration
gradient = the amount diffusing in down its electrical gradient.

EK = RT . loge [K+]i Nernst Equation

zF [K+]o

Normally, [K+]i : [K+]o is = 35 : 1

It is important for you to realize that both a raised extracellular K+ level (hyperkalemia)
and a low extracellular K+ level (hypokalemia) can have profound effects on the RMP
ultimately leading to fatal arrhythmias and cardiac arrest.

In ventricular myocytes the EK = -95 mV but the actual RMP = -85 mV. This is because the
myocyte membrane is very slightly permeable to Na+; and so, some Na+ flow into the cell
down its electrochemical gradient. This Na current is called the background current ib and it
results in the RMP being ~10 mV less negative than E K. Consequently the inside of the
myocyte is not negative enough to balance the outward flow of K+ resulting in a continuous
trickle of K+ ions diffusing out. If this was allowed to continue the concentration gradients for
K+ and Na+ would eventually dissipate (and there would be no membrane potential at all). To
make sure this does not happen, the Na+-K+ ATPase pump comes into play. It pumps out Na+
and pumps back in K+ (using ATP as its energy source). The importance of the pump cannot
be overestimated. This pump maintains the ionic gradients (just as it does in neurons and in
skeletal muscles). However in the heart, the Na gradient is also important because the Na
gradient is used by various ion exchangers to transport Ca++ and H+ ions across the cell
membrane.

At this stage some of the pumps and exchangers that play an important role in the excitability
of cardiac cells will be briefly described.

3
Role of Pump and Exchangers

Sodium pump (Na+-K+ ATPase)

Active pump, using ATP. 3Na+ move out of the cell for every 2K+ pumped in. Changes in
[Na+]i and [K+]o alter the pumping rate. It is very important in maintaining the Na gradient.
This Na gradient then ensures that the exchangers below work.

Na+-H+ Exchanger

Regulates intracellular pH. Transports H+ out of the cell in exchange for Na+ which flows
into the cell down the gradient set up by the Na pump. Control of intracellular H+ is very
important since protein conformation is altered by abnormal H+ levels.

Ca++ Transporters: Na-Ca Exchanger and Ca -ATPase pump

In the Na-Ca exchanger, 3Na+ enter the cell and 1Ca++ leaves. (Ca++ enter the cell during the
plateau phase of the cardiac action potential). The exchanger is driven by the Na+
concentration gradient (maintained by the Na pump). The Na-Ca exchanger is responsible for
expelling most of the Ca++ out of the myocyte. The rest is taken up into the sarcoplasmic
reticulum by the Ca-ATPase pump. This pump pumps Ca against its concentration gradient
back into the sarcoplasmic reticulum from the cytosol.
Digoxin, a drug used in heart failure improves the contractility of the heart by indirectly
increasing intracellular Ca++. It works by blocking the Na pump such that the Na gradient is
reduced, resulting in less Ca being expelled from the myocyte and consequently intracellular
Ca++ levels increase and the contractile force is enhanced.

Why some channels are called rectifiers

The conductances (permeability) of some ion channels (notably K +) and their ability to carry current may
depend on the actual membrane potential of the cell. This property is called rectification and the currents
flowing through these channels are said to be rectified currents. Certain K channels are called rectifiers. One set
of K channels prefer to be in the open state when the membrane is depolarized. The resulting outward K+
current is called an outward rectifying current and this particular channel is called the outward rectifier. The
current flowing through this channel is trying to rectify the situation (i.e. to repolarize) and bring back the
membrane potential to its resting level.
Another K channel, open at resting potentials and responsible for the trickle of K + out of the cells, is the inward
rectifier channel. The current flowing through this is i K1. When the membrane is depolarized the conductance of
this channel falls, resulting in reduced iK1. This is advantageous since during the action potential, the
conductance of this channel falls, iK1 is reduced and less K+ will trickle out. This mechanism is important in
conserving the intracellular [K+] during the long cardiac action potential.

4
Ventricular Myocyte Action Potential Cardiac Action Potential

The cardiac action potential has 5 distinct phases (0, 1, 2, 3 and 4).

Phase 1 Partial Repolarization

+70 ENa
Phase 2 Plateau
Phase 0
mV 0 Phase 3
Depolarization
Repolarization
Phase 4
-95 EK

300 ms

Figure 2 A typical cardiac action potential recorded from a ventricular myocyte.

Phase 4 Resting Stable potential at -85 mV

Phase 0 Rapid Depolarization inward Na+ current iNa

When voltage-gated Na channels open - Na+ rush in (iNa), M.P. becomes +ve
(~ +20 mV) and approaches ENa but does not reach it because Na
inactivation occurs.
This channel (like those in nerves and skeletal muscles) possesses two gates
m and h. At rest, the m gate is closed but the h gate is open; when the
membrane is depolarized by ionic currents, the m gate (which has a voltage
sensor in it) opens briefly allowing Na+ to enter. The resulting depolarization
meanwhile starts to close the h gates triggering Na inactivation. (During
repolarization the m gate closes but the h gate starts to open again; and the
channel returns to its resting state).

Another reason for not reaching ENa is that the depolarization also opens voltage-gated K+
channels which cause an outward K+ current (ito) see below.

Phase 1 Initial Rapid Repolarization outward K+ current ito

The opening of the voltage-gated K+ channels causes K+ to flow out of the cell
through the outward rectifier channel. This outward current starts to repolarize
the cell. (i.e. it is trying to rectify the situation). The current is denoted ito (to
= transient outward). The membrane potential is partially repolarized to just
above zero.

(Meanwhile the inward rectifier K channels are closing because of the

depolarization of the membrane and iK1 is reduced. This effect helps to
conserve intracellular K+).

5
This initial rapid repolarisation is shortlived and is followed by a much slower rate of
repolarisation forming the plateau phase of the action potential.

Phase 2 Plateau phase inward Ca++ iCa

This phase lasting 100 - 200 ms, where the membrane is repolarizing at a very
slow rate, is unique to cardiac cells. It is due to a small but long lasting Ca
influx, iCa (carrying Ca++ ions into the cell) which prevents the myocyte from
repolarizing too rapidly. The Ca channels responsible for this current are the
L-type channels. These channels are voltage-gated but open very slowly in
response to a depolarization. Once open, they then inactivate very slowly. The
Ca current is small but is sufficient to counterbalance the repolarizing effect of
the K+ current (ito) and so holding the membrane potential at around 0 mV for
a long time. Why is this beneficial to us?

During the plateau, the membrane potential is around 0 mV, Na channels

remain inactivated and another action potential cannot be generated.

The Ca++ that enters the myocyte during the plateau phase triggers the release of Ca++ from
the sarcoplasmic reticulum. This Ca-induced Ca++ release mechanism is responsible for the
large increase in cytosolic [Ca++] which is essential for muscle contraction.
Ca++ is removed from the cytosol by pumping it back into the sarcoplasmic reticulum using
the Ca++-ATPase pump or back into the extracellular fluid by the Na+-Ca++ exchanger.

Phase 3 Rapid repolarization outward K+ iK

This period of rapid repolarisation after the plateau phase is due to the opening
of another set of K+ channels called the delayed rectifiers and the current is
iK. These channels open in response to a depolarization but they open very
slowly. Since the K current is trying to repolarise the membrane and bring it
back to resting levels they are also called rectifier currents and the delayed
means they open very slowly.
In the meantime the Ca channels have closed.

The cell membrane potential now returns back to its resting level.

Phase 4 Resting potential

This is the interval between action potentials. In atrial and ventricular myocytes the
resting potential is stable and ionic permeabilities are not changing.

6
 Figure 3 Currents responsible for the different phases of the cardiac action
potential. (Rhoades and Bell: Medical Physiology)

Propagation of Action Potentials from Myocyte to Myocyte

In cardiac muscles an action potential generated in one cardiac (myocardial) cell can
propagate into an adjacent myocardial cell. This is completely different from the situation in
skeletal muscles where action potentials cannot propagate from one muscle fibre to another.
An individual skeletal muscle fibre can only generate action potentials when the nerve
supplying that particular muscle fibre is stimulated. This major difference between cardiac
and skeletal muscle is due to the nature of connection between muscle cells. Myocardial cells
(unlike skeletal) are branched and rather than running the full length of the heart they are

7
short and are interconnected to other myocardial cells via intercalated disks. These
intercalated disks are composed of desmosomes which hold the cells together; and gap
junctions which allow ions to move from one cell to the next. This means then that
myocardial cells (unlike skeletal muscle fibres which do not have these gap junctions) are
electrically coupled. Therefore, an action potential in one myocardial cell will generate
ionic currents that can flow through the gap junctions to the next myocardial cell. This ionic
current can then cause a depolarization which will trigger the opening of voltage-gated Na
channels in this adjacent myocyte, thereby triggering an action potential in that cell.

The ionic currents caused by an action potential in one cell are usually strong enough to
depolarize the adjacent myocyte sufficiently such that voltage-gated Na channels open and an
all-or-none action potential is generated in the adjacent cell. In this way, cardiac action
potentials are propagated from cell to cell through the conducting system and into the atrial
and ventricular myocardium.

(Pathological conditions arise in which the ionic currents generated during an action
potential are not of sufficient amplitude to depolarize adjacent cells and failure of conduction
in some parts of the heart will then occur, often giving rise to cardiac arrhythmias).

The huge advantage of this is that when an action potential is initiated in the SA node, it then
spreads throughout all the myocardial cells of the heart and the heart then contracts as a
whole; in other words the heart behaves as a syncytium. Why is this so important? Well
imagine if some part of the heart contracted, then a few milliseconds later, another part
contracted and so on (which can happen in skeletal muscles) the overall contraction of the
heart would not be strong enough to pump the blood out i.e. the heart could not function as a
pump. Therefore it is absolutely essential that the heart contracts as a single unit so that it can
function efficiently as a pump.

Refractory Period

The myocyte is electrically inexcitable, or refractory throughout the long period of

depolarization which starts when the h gates close (Na channels are inactivated). During the
absolute refractory time which lasts throughout the plateau phase (~ 250 300 ms) no
stimulus (i.e. local current) whatever its size can evoke another action potential. This is
followed by the relative refractory period when stimuli that would exceed the normal
threshold (i.e. stronger stimuli) can initiate an action potential. SN (in figure 4) denotes the
supernormal period which is not seen in ventricular myocytes. The long refractory period of
myocardial cells is due to the prolonged plateau phase, which delays the return of the
membrane potential to its resting value, and to the slow rate of channel recovery after the
membrane has repolarized.

8
 1
2
0
Absolute RP
mV 0
3
Relative RP
-85
4 4

0 250 300 350

Time (ms)

Figure 4 A cardiac action potential showing absolute and relative refractory periods.

Advantages of a prolonged refractory period

1. A long refractory period ensures that conduction proceeds in one direction. If a cell did not
become refractory it would be possible for the action potential to proceed backwards to re-
excite a cell that had just been depolarized. This would completely disrupt the normal
excitation of the heart and lead to abnormal electrical circuits being formed causing
arrhythmias.

2. In skeletal muscles, the refractory period of the muscle cell is very short (~5ms) whereas
the duration of the mechanical twitch is ~ 100 ms. This means that a repeatedly stimulated
muscle cell could generate several action potentials which would result in a large sustained
tetanic response. These are useful in skeletal muscles for maintaining tension; however, in the
heart such sustained contractions would be fatal. The heart is a pump and needs to contract
and relax rhythmically. Fortunately tetanic contractions cannot occur in the heart simply
because the plateau phase has prolonged the cardiac action potential such that the muscle
mechanical response is practically over by the time the myocytes have become fully
repolarized and ready to be excited again. This concept is illustrated in the next figure.

9
Figure 5 Relationship between the action potential and the muscle twitch in a skeletal muscle
(upper traces) and in cardiac muscle (lower traces)

The upper traces show the time relationship between the muscle action potential and the
muscle twitch (upper left) and the effects of increasing the frequency of stimulation of the
muscle. Since the refractory period is short several muscle twitches can summate to give one
large tetanic contraction (upper right). The lower trace shows the same scenario in cardiac
muscle. By the time the myocyte has recovered its excitability the muscle twitch is practically
over. Tetanic contractions cannot therefore occur.

The cardiac action potential from the ventricular myocyte has been described in detail.
The action potential in the SA node (and AV node) differs in many respects from that in
myocytes.

10
Sinoatrial Node
R.M.P: Unstable, fluctuates between 60 and -40 mV

This resting potential decays spontaneously with time and is called the pacemaker
potential or the slow diastolic potential. When the pacemaker potential reaches a threshold
of -40 mV an action potential is triggered. The fact that the membrane potential is unstable
and slowly depolarizes explains why action potentials are generated spontaneously in these
cells. This is ultimately
responsible +20 for the heart beat.

0
iCa iK
Membrane Potential

-20 0 3

-40

if i C 4
a

-60

Pacemaker Action Potential

Potential

Figure 6 A typical action potential from the SA node showing the various currents.

The above is a typical SA node action potential. It differs from the myocyte action potential
in that there is no plateau phase and phase 4 is unstable. Phase 4 is the pacemaker potential
and it decays with time.

Phase 4 Pacemaker Potential inward if and inward iCa current

The if current is mainly a Na+ current. f refers to funny since these channels
open when the inside is relatively negative (polarized); normally Na channels
open in response to a depolarization of the cell (hence the name funny as in
funny peculiar).

The iCa current is due to opening of T-type Ca channels.

(T because they open very transiently). These start opening when the
pacemaker potential becomes less negative i.e. they open in response to a
depolarization; and they contribute further to the depolarization.

Phase 0 inward Ca current

As the membrane depolarizes, if channels start to close. When the membrane

potential reaches the threshold value (-40 mV) L-type Ca channels open and
Ca++ enter causing upstroke of the action potential.
Note that this is due to an inward Ca++ current, not Na+!

11
Phase 3 Outward K current

Repolarization is due to closure of Ca channels and opening of K channels. As

membrane becomes repolarized the if channels start to open again. When fully
opened the membrane starts to spontaneously depolarize again.
Refractory Period

In the SA node the absolute refractory period extends to almost the end of the nodal action
potential and the relative refractory period extends well into phase 4.

Action Potentials from different parts of the Heart

Figure 8 Action potentials from different parts of the heart (A is a typical

ventricular myocyte); B is from the SA node and C is from an atrial
myocyte. (Medical Physiology Rhoades and Bell)

Note:

Atrial myocytes
Same shape as ventricular myocytes but shorter duration due to a briefer plateau phase.

AV node (not illustrated):

Pacemaker potential which decays at a slower rate than the SA node

12
Transmission of Excitation through the heart

Figure 9 The conducting pathways of the heart (Rhoades and Bell: Medical
Physiology)

Action potentials, initiated in the SA node are propagated through internodal fibres to excite
atrial myocytes. This wave of depolarization then invades the AV node but its conduction
through the AV node is slowed (0.05m/s). This delay allows time for the atria to complete
their contraction before the ventricles are stimulated to contract. Next the wave of
depolarization travels down the bundle of His (left and right branches) with a speed of 2 4
m/s. The left side of the septum is depolarized slightly before the right.

Figure 10 Spread of the wave of excitation through the heart showing the times the
various parts are activated. (Rhoades and Bell: Medical Physiology)

13
The Purkinje fibres are then depolarized and due to their extensive branching the wave of
depolarization spreads very quickly through the ventricular myocardium. Initially the apex of
the heart is excited and from the apex the action potentials spread upward and outward, first
depolarizing the endocardium and then the epicardium. This causes the ventricular
contraction to begin at the apex and move towards the base of the heart.

This spread of excitation through the heart is brought about by the ionic currents that act
ahead of the action potential. An action potential in one cell will set up these local ionic
currents which flow easily through gap junctions to excite the adjacent cell and cause their
voltage-gated Na channels to open, thereby triggering action potentials in these adjacent cells.
The local currents have to be sufficiently strong to depolarize the adjacent cells to threshold.
The action potential proceeds in one direction because of the refractory period.

The delay at the AV node: advantages and disadvantages

The atria and the ventricles are electrically isolated from each other by the annulus
fibrosus (a connective tissue ring separating the atria and ventricles). The AV node,
located just above the annulus fibrosus is the only electrical contact between the atria
and the ventricle. Conduction through the AV node is very slow (0.05 m/s) because of
the slow rate of rise of the AV action potential and higher electrical resistance
between cells (due to a smaller number of gap junctions).
The disadvantage of having a slow rise of the action potential (and a smaller
amplitude) compared with other parts of the heart is that the local currents formed are
not as strong, and being weaker they are more likely to fail to excite the regions
ahead. Therefore, conduction through the AV node is quite precarious it is much
more likely to fail here than in any other part of the conducting system. The AV node
is said to have a low safety factor. Failure of conduction through the AV node is an
important cause of AV block (see later).

However there are distinct advantages to having slowed conduction through the AV
node and also to the AV node having a long refractory period. It allows time for the
atria to contract before the ventricles start to contract. This is important since atrial
contractions pushes a further volume of blood into the ventricles to be ejected.
Another big advantage is that should the atria develop an abnormally fast rhythm due
to disease or to the effects of drugs, many of these atrial depolarizations reaching the
AV node will find the AV node refractory. Not every atrial depolarization will be
transmitted to the ventricles. This prevents a rapid abnormal atrial rhythm from
inducing a too rapid rhythm in the ventricles; thus protecting the ventricles. A rapid
ventricular beat would interfere with filling and cardiac output could dramatically
rapidly.

14
Hierarchy of Pacemakers
The SA node in the innervated heart fires action potentials at a rate of ~ 60 75/min. This is
called the normal sinus rhythm of the heart. The firing rate of the SA node is related to the
slope of the pacemaker potential: the steeper the slope the faster the beat. In a heart which has
no neural innervation (such as a transplanted heart) the intrinsic firing rate of the SA node
would be ~ 100 /min since the normal inhibitory tone exerted by the parasympathetic system
would be absent.
If the SA node is damaged, then other parts of the conducting system can take over the
pacemaker function. The AV node would fire action potentials at a rate of ~ 50/min
(pacemaker potential slope is not as steep as in the SA node), the bundle of His at 40/min
and the Purkinje fibres at ~15/min. Therefore, within the electrical system of the heart there is
a gradient of pacemakers, with the SA node (with its highest intrinsic firing frequency) being
at the top. Consequently, the SA node determines the HR.

Although action potentials are only generated spontaneously in the SA node in healthy
individuals, damaged ventricular muscle cells (as can occur after a myocardial infarction)
can start to generate action potentials themselves. This mechanism is one of the major
causes of arrhythmias.

Regulation of the Heart Rate

HR is controlled by the ANS: both parasympathetic (PS) and sympathetic nerves.

Both are tonically active on the heart, although at rest, the parasympathetic tone
predominates.

Effects of Parasympathetic activity: HR Bradycardia

PS fibres supplying the heart, are found in the right and left vagus nerves; their cell bodies are
in the vagal motor nuclei. Postganglionic fibres are within the myocardium itself and the
neurotransmitter released is acetylcholine.

ACh binds to muscarinic (M2) receptors on the heart. The action is terminated by
acetylcholinesterase. ACh reduces the heart rate (negative chronotropic effect).

Mechanism of bradycardia:

rate of decay of the pacemaker potential

The pacemaker potential takes longer to reach threshold and HR falls.

ACh hyperpolarizes the SA node and also reduces the if and iCa currents. How it does this is
shown on the next page.

15
Cellular Mode of Action of Acetylcholine

Acetylcholine

Activates M2 receptors

Activates GK protein Activates Gi protein

adenylate cyclase
Opening of KACh channel

cAMP

Increases iK
protein kinase A

activation of if and iCa channels

Hyperpolarizes SA node

if and iCa currents

Heart Rate

The opening of the K channels is fast which explains why the vagus quickly slows down the
heart. Examples of vagal bradycardia include:

Slowing of the heart during expiration (sinus arrhythmia)

Low heart rate of a trained athlete
Slowing of the heart during a dive (diving reflex)
Transient arrest of the heart at the onset of fainting (vasovagal attack)

16
Effects of sympathetic activity: HR (+ ve chronotropic effect)

Force of contraction (+ve inotropic effect)

Chronotropic Effect

1. rate of pacemaker depolarization threshold is reached sooner

2. Increased conduction through AV node
3. Reduced duration of atrial and ventricular myocyte action potentials

Sympathetic activity releases NE which binds to 1 receptors on cardiac cells.

Cellular Mode of Action of Norepinephrine and Epinephrine

Norepinephrine and Epinephrine

1 receptors on the heart

cAMP

Phosphorylation of if and Ca channels

if, iCa currents

rate of depolarization

Heart Rate

17
Figure 11

Effects of sympathetic stimulation (trace a) and parasympathetic stimulation (trace c) on the

SA node action potential. Trace b is the control trace.
(Medical Physiology Rhoades and Bell)

18
Clinical correlates

Alternative conducting pathways

Abnormal electrical connections sometimes link the atria and the ventricles these accessory
pathways include the bundle of Kent which are strands of atrial myocardium that cross the
annulus fibrosus at various locations. These abnormal pathways are generally dormant, but
can become active and provide alternate pathways to the slower conducting pathway through
the AV node. The bundle of Kent explains the arrhythmias seen in the Wolff Parkinson
White syndrome.

Effects of altered ionic environment

Hyperkalemia ([K+]o > 5.5 mM) Cardiac Arrhythmias Cardiac arrest

Resting Membrane Potential is reduced (less negative). At an RMP of -50 mV almost all the
voltage-gated Na channels are closed; whereas at 70 mV some are still open. As a result the
cardiac action potential is more dependent on the Ca current and consequently is smaller in
amplitude. This results in the local currents generated being weaker and unable to excite the
adjacent myocytes. This favors the formation of arrhythmias, particularly ventricular
fibrillation and cardiac arrest.
Hyperkalemia occurs as a result of tissue ischemia (myocardial infarction), renal failure,
acidosis or potassium overload.

Hypokalemia ([K+]o < 3.5 mM) Arrhythmias Cardiac arrest

RMP is increased (more negative). This triggers afterdepolarizations. Afterdepolarizations

occur when a normal action potential triggers extra abnormal depolarizations which may lead
to arrhythmias.

Changes in [K+] levels affect the permeability of the Ca channels and it is often the
disturbance of the Ca channel that results in changes in excitability of the myocardium. Note
that both hypo- and hyperkalemia cause arrhythmias which could lead to cardiac arrest.

H+ and Ischemia
Intracellular H+ ions compete with Ca for the troponin binding sites. Therefore, an increase
in intracellular [H+] resulting from, say, ischemia, weakens cardiac contractions.

19