<s>
The	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
is	O
a	O
brief	O
change	O
in	O
voltage	O
(	O
membrane	O
potential	O
)	O
across	O
the	O
cell	O
membrane	O
of	O
heart	O
cells	O
.	O
</s>
<s>
The	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
differs	O
from	O
action	B-Algorithm
potentials	I-Algorithm
found	O
in	O
other	O
types	O
of	O
electrically	O
excitable	O
cells	O
,	O
such	O
as	O
nerves	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
also	O
vary	O
within	O
the	O
heart	O
;	O
this	O
is	O
due	O
to	O
the	O
presence	O
of	O
different	O
ion	O
channels	O
in	O
different	O
cells	O
.	O
</s>
<s>
Unlike	O
the	O
action	B-Algorithm
potential	I-Algorithm
in	O
skeletal	O
muscle	O
cells	O
,	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
is	O
not	O
initiated	O
by	O
nervous	O
activity	O
.	O
</s>
<s>
Instead	O
,	O
it	O
arises	O
from	O
a	O
group	O
of	O
specialized	O
cells	O
known	O
as	O
pacemaker	B-Algorithm
cells	I-Algorithm
,	O
that	O
have	O
automatic	O
action	B-Algorithm
potential	I-Algorithm
generation	O
capability	O
.	O
</s>
<s>
In	O
healthy	O
hearts	O
,	O
these	O
cells	O
form	O
the	O
cardiac	B-Algorithm
pacemaker	I-Algorithm
and	O
are	O
found	O
in	O
the	O
sinoatrial	O
node	O
in	O
the	O
right	O
atrium	O
.	O
</s>
<s>
They	O
produce	O
roughly	O
60100	O
action	B-Algorithm
potentials	I-Algorithm
every	O
minute	O
.	O
</s>
<s>
The	O
action	B-Algorithm
potential	I-Algorithm
passes	O
along	O
the	O
cell	O
membrane	O
causing	O
the	O
cell	O
to	O
contract	O
,	O
therefore	O
the	O
activity	O
of	O
the	O
sinoatrial	O
node	O
results	O
in	O
a	O
resting	O
heart	O
rate	O
of	O
roughly	O
60100	O
beats	O
per	O
minute	O
.	O
</s>
<s>
All	O
cardiac	O
muscle	O
cells	O
are	O
electrically	O
linked	O
to	O
one	O
another	O
,	O
by	O
intercalated	O
discs	O
which	O
allow	O
the	O
action	B-Algorithm
potential	I-Algorithm
to	O
pass	O
from	O
one	O
cell	O
to	O
the	O
next	O
.	O
</s>
<s>
Rate	O
dependence	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
is	O
a	O
fundamental	O
property	O
of	O
cardiac	O
cells	O
and	O
alterations	O
can	O
lead	O
to	O
severe	O
cardiac	O
diseases	O
including	O
cardiac	B-Application
arrhythmia	I-Application
and	O
sometimes	O
sudden	O
death	O
.	O
</s>
<s>
Action	B-Algorithm
potential	I-Algorithm
activity	O
within	O
the	O
heart	O
can	O
be	O
recorded	O
to	O
produce	O
an	O
electrocardiogram	B-Application
(	O
ECG	B-Application
)	O
.	O
</s>
<s>
This	O
is	O
a	O
series	O
of	O
upward	O
and	O
downward	O
spikes	B-Algorithm
(	O
labelled	O
P	O
,	O
Q	O
,	O
R	O
,	O
S	O
and	O
T	O
)	O
that	O
represent	O
the	O
depolarization	O
(	O
voltage	O
becoming	O
more	O
positive	O
)	O
and	O
repolarization	O
(	O
voltage	O
becoming	O
more	O
negative	O
)	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
in	O
the	O
atria	O
and	O
ventricles	O
.	O
</s>
<s>
The	O
action	B-Algorithm
potential	I-Algorithm
begins	O
with	O
the	O
voltage	O
becoming	O
more	O
positive	O
;	O
this	O
is	O
known	O
as	O
depolarization	O
and	O
is	O
mainly	O
due	O
to	O
the	O
opening	O
of	O
sodium	O
channels	O
that	O
allow	O
Na+	O
to	O
flow	O
into	O
the	O
cell	O
.	O
</s>
<s>
After	O
a	O
delay	O
(	O
known	O
as	O
the	O
absolute	O
refractory	O
period	O
)	O
,	O
the	O
action	B-Algorithm
potential	I-Algorithm
terminates	O
as	O
potassium	O
channels	O
open	O
,	O
allowing	O
K+	O
to	O
leave	O
the	O
cell	O
and	O
causing	O
the	O
membrane	O
potential	O
to	O
return	O
to	O
negative	O
,	O
this	O
is	O
known	O
as	O
repolarization	O
.	O
</s>
<s>
Release	O
of	O
Ca2+	O
from	O
the	O
SR	O
,	O
via	O
a	O
process	O
called	O
calcium-induced	O
calcium	O
release	O
,	O
is	O
vital	O
for	O
the	O
plateau	O
phase	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
(	O
see	O
phase	O
2	O
,	O
below	O
)	O
and	O
is	O
a	O
fundamental	O
step	O
in	O
cardiac	O
excitation-contraction	O
coupling	O
.	O
</s>
<s>
There	O
are	O
important	O
physiological	O
differences	O
between	O
the	O
pacemaker	B-Algorithm
cells	I-Algorithm
of	O
the	O
sinoatrial	O
node	O
,	O
that	O
spontaneously	O
generate	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
and	O
those	O
non-pacemaker	O
cells	O
that	O
simply	O
conduct	O
it	O
,	O
such	O
as	O
ventricular	O
myocytes	O
)	O
.	O
</s>
<s>
The	O
specific	O
differences	O
in	O
the	O
types	O
of	O
ion	O
channels	O
expressed	O
and	O
mechanisms	O
by	O
which	O
they	O
are	O
activated	O
results	O
in	O
differences	O
in	O
the	O
configuration	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
waveform	O
,	O
as	O
shown	O
in	O
figure	O
2	O
.	O
</s>
<s>
Cardiac	O
automaticity	O
also	O
known	O
as	O
autorhythmicity	O
,	O
is	O
the	O
property	O
of	O
the	O
specialized	O
conductive	B-Algorithm
muscle	O
cells	O
of	O
the	O
heart	O
to	O
generate	O
spontaneous	O
cardiac	B-Algorithm
action	I-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
Automaticity	O
can	O
be	O
normal	O
or	O
abnormal	O
,	O
caused	O
by	O
temporary	O
ion	O
channel	O
characteristic	O
changes	O
such	O
as	O
certain	O
medication	O
usage	O
,	O
or	O
in	O
the	O
case	O
of	O
abnormal	O
automaticity	O
the	O
changes	O
are	O
in	O
electrotonic	B-Algorithm
environment	I-Algorithm
,	O
caused	O
,	O
for	O
example	O
,	O
by	O
myocardial	O
infarction	O
.	O
</s>
<s>
The	O
standard	O
model	O
used	O
to	O
understand	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
is	O
that	O
of	O
the	O
ventricular	O
myocyte	O
.	O
</s>
<s>
Outlined	O
below	O
are	O
the	O
five	O
phases	O
of	O
the	O
ventricular	O
myocyte	O
action	B-Algorithm
potential	I-Algorithm
,	O
with	O
reference	O
also	O
to	O
the	O
SAN	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
Therefore	O
,	O
the	O
resting	O
membrane	O
potential	O
is	O
mostly	O
equal	O
to	O
K+	O
equilibrium	B-Algorithm
potential	I-Algorithm
and	O
can	O
be	O
calculated	O
using	O
the	O
Goldman-Hodgkin-Katz	O
voltage	O
equation	O
.	O
</s>
<s>
However	O
,	O
pacemaker	B-Algorithm
cells	I-Algorithm
are	O
never	O
at	O
rest	O
.	O
</s>
<s>
In	O
these	O
cells	O
,	O
phase	O
4	O
is	O
also	O
known	O
as	O
the	O
pacemaker	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
During	O
this	O
phase	O
,	O
the	O
membrane	O
potential	O
slowly	O
becomes	O
more	O
positive	O
,	O
until	O
it	O
reaches	O
a	O
set	O
value	O
(	O
around	O
-40	O
mV	O
;	O
known	O
as	O
the	O
threshold	B-Algorithm
potential	I-Algorithm
)	O
or	O
until	O
it	O
is	O
depolarized	O
by	O
another	O
action	B-Algorithm
potential	I-Algorithm
,	O
coming	O
from	O
a	O
neighboring	O
cell	O
.	O
</s>
<s>
The	O
pacemaker	B-Algorithm
potential	I-Algorithm
is	O
thought	O
to	O
be	O
due	O
to	O
a	O
group	O
of	O
channels	O
,	O
referred	O
to	O
as	O
HCN	O
channels	O
(	O
Hyperpolarization-activated	O
cyclic	O
nucleotide-gated	O
)	O
.	O
</s>
<s>
immediately	O
after	O
phase	O
3	O
of	O
the	O
previous	O
action	B-Algorithm
potential	I-Algorithm
;	O
see	O
below	O
)	O
and	O
allow	O
the	O
passage	O
of	O
both	O
K+	O
and	O
Na+	O
into	O
the	O
cell	O
.	O
</s>
<s>
Due	O
to	O
their	O
unusual	O
property	O
of	O
being	O
activated	O
by	O
very	O
negative	O
membrane	O
potentials	O
,	O
the	O
movement	O
of	O
ions	O
through	O
the	O
HCN	O
channels	O
is	O
referred	O
to	O
as	O
the	O
funny	B-Algorithm
current	I-Algorithm
(	O
see	O
below	O
)	O
.	O
</s>
<s>
Another	O
hypothesis	O
regarding	O
the	O
pacemaker	B-Algorithm
potential	I-Algorithm
is	O
the	O
'	O
calcium	O
clock	O
 '	O
.	O
</s>
<s>
These	O
channels	O
are	O
activated	O
when	O
an	O
action	B-Algorithm
potential	I-Algorithm
arrives	O
from	O
a	O
neighbouring	O
cell	O
,	O
through	O
gap	O
junctions	O
.	O
</s>
<s>
If	O
this	O
increased	O
voltage	O
reaches	O
the	O
threshold	B-Algorithm
potential	I-Algorithm
(	O
approximately	O
70mV	O
)	O
it	O
causes	O
the	O
Na+	O
channels	O
to	O
open	O
.	O
</s>
<s>
towards	O
the	O
Na+	O
equilibrium	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
However	O
,	O
if	O
the	O
initial	O
stimulus	O
is	O
not	O
strong	O
enough	O
,	O
and	O
the	O
threshold	B-Algorithm
potential	I-Algorithm
is	O
not	O
reached	O
,	O
the	O
rapid	O
sodium	O
channels	O
will	O
not	O
be	O
activated	O
and	O
an	O
action	B-Algorithm
potential	I-Algorithm
will	O
not	O
be	O
produced	O
;	O
this	O
is	O
known	O
as	O
the	O
all-or-none	O
law	O
.	O
</s>
<s>
The	O
slope	O
of	O
phase	O
0	O
on	O
the	O
action	B-Algorithm
potential	I-Algorithm
waveform	O
(	O
see	O
figure	O
2	O
)	O
represents	O
the	O
maximum	O
rate	O
of	O
voltage	O
change	O
of	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
and	O
is	O
known	O
as	O
dV/dtmax	O
.	O
</s>
<s>
In	O
pacemaker	B-Algorithm
cells	I-Algorithm
(	O
e.g.	O
</s>
<s>
These	O
channels	O
are	O
also	O
activated	O
by	O
an	O
increase	O
in	O
voltage	O
,	O
however	O
this	O
time	O
it	O
is	O
either	O
due	O
to	O
the	O
pacemaker	B-Algorithm
potential	I-Algorithm
(	O
phase	O
4	O
)	O
or	O
an	O
oncoming	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
The	O
L-type	O
calcium	O
channels	O
are	O
activated	O
more	O
slowly	O
than	O
the	O
sodium	O
channels	O
,	O
therefore	O
,	O
the	O
depolarization	O
slope	O
in	O
the	O
pacemaker	O
action	B-Algorithm
potential	I-Algorithm
waveform	O
is	O
less	O
steep	O
than	O
that	O
in	O
the	O
non-pacemaker	O
action	B-Algorithm
potential	I-Algorithm
waveform	O
.	O
</s>
<s>
This	O
is	O
referred	O
to	O
as	O
a	O
'	O
notch	O
 '	O
on	O
the	O
action	B-Algorithm
potential	I-Algorithm
waveform	O
.	O
</s>
<s>
There	O
is	O
no	O
obvious	O
phase	O
1	O
present	O
in	O
pacemaker	B-Algorithm
cells	I-Algorithm
.	O
</s>
<s>
This	O
phase	O
is	O
responsible	O
for	O
the	O
large	O
duration	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
and	O
is	O
important	O
in	O
preventing	O
irregular	B-Application
heartbeat	I-Application
(	O
cardiac	B-Application
arrhythmia	I-Application
)	O
.	O
</s>
<s>
There	O
is	O
no	O
plateau	O
phase	O
present	O
in	O
pacemaker	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
During	O
phase	O
3	O
(	O
the	O
"	O
rapid	O
repolarization	O
"	O
phase	O
)	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
,	O
the	O
L-type	O
Ca2+	O
channels	O
close	O
,	O
while	O
the	O
slow	O
delayed	O
rectifier	O
(	O
IKs	O
)	O
K+	O
channels	O
remain	O
open	O
as	O
more	O
potassium	O
leak	O
channels	O
open	O
.	O
</s>
<s>
Cardiac	O
cells	O
have	O
two	O
refractory	O
periods	O
,	O
the	O
first	O
from	O
the	O
beginning	O
of	O
phase	O
0	O
until	O
part	O
way	O
through	O
phase	O
3	O
;	O
this	O
is	O
known	O
as	O
the	O
absolute	O
refractory	O
period	O
during	O
which	O
it	O
is	O
impossible	O
for	O
the	O
cell	O
to	O
produce	O
another	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
This	O
is	O
immediately	O
followed	O
,	O
until	O
the	O
end	O
of	O
phase	O
3	O
,	O
by	O
a	O
relative	O
refractory	O
period	O
,	O
during	O
which	O
a	O
stronger-than-usual	O
stimulus	O
is	O
required	O
to	O
produce	O
another	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
The	O
rapid	O
depolarization	O
of	O
the	O
cell	O
,	O
during	O
phase	O
0	O
,	O
causes	O
the	O
membrane	O
potential	O
to	O
approach	O
sodium	O
's	O
equilibrium	B-Algorithm
potential	I-Algorithm
(	O
i.e.	O
</s>
<s>
Because	O
some	O
of	O
the	O
voltage-gated	O
sodium	O
ion	O
channels	O
have	O
recovered	O
and	O
the	O
voltage-gated	O
potassium	O
ion	O
channels	O
remain	O
open	O
,	O
it	O
is	O
possible	O
to	O
initiate	O
another	O
action	B-Algorithm
potential	I-Algorithm
if	O
the	O
stimulus	O
is	O
stronger	O
than	O
a	O
stimulus	O
which	O
can	O
fire	O
an	O
action	B-Algorithm
potential	I-Algorithm
when	O
the	O
membrane	O
is	O
at	O
rest	O
.	O
</s>
<s>
Gap	O
junctions	O
allow	O
the	O
action	B-Algorithm
potential	I-Algorithm
to	O
be	O
transferred	O
from	O
one	O
cell	O
to	O
the	O
next	O
(	O
they	O
are	O
said	O
to	O
electrically	O
couple	O
neighbouring	O
cardiac	O
cells	O
)	O
.	O
</s>
<s>
This	O
increased	O
potassium	O
in	O
the	O
neighbour	O
cell	O
causes	O
the	O
membrane	O
potential	O
to	O
increase	O
slightly	O
,	O
activating	O
the	O
sodium	O
channels	O
and	O
initiating	O
an	O
action	B-Algorithm
potential	I-Algorithm
in	O
this	O
cell	O
.	O
</s>
<s>
(	O
A	O
brief	O
chemical	O
gradient	O
driven	O
efflux	O
of	O
Na+	O
through	O
the	O
connexon	O
at	O
peak	O
depolarization	O
causes	O
the	O
conduction	B-Algorithm
of	O
cell	O
to	O
cell	O
depolarization	O
,	O
not	O
potassium	O
.	O
)	O
</s>
<s>
These	O
connections	O
allow	O
for	O
the	O
rapid	O
conduction	B-Algorithm
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
throughout	O
the	O
heart	O
and	O
are	O
responsible	O
for	O
allowing	O
all	O
of	O
the	O
cells	O
in	O
the	O
atria	O
to	O
contract	O
together	O
as	O
well	O
as	O
all	O
of	O
the	O
cells	O
in	O
the	O
ventricles	O
.	O
</s>
<s>
Uncoordinated	O
contraction	O
of	O
heart	O
muscles	O
is	O
the	O
basis	O
for	O
arrhythmia	B-Application
and	O
heart	O
failure	O
.	O
</s>
<s>
Figure	O
3	O
shows	O
the	O
important	O
ion	O
channels	O
involved	O
in	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
,	O
the	O
current	O
(	O
ions	O
)	O
that	O
flows	O
through	O
the	O
channels	O
,	O
their	O
main	O
protein	O
subunits	O
(	O
building	O
blocks	O
of	O
the	O
channel	O
)	O
,	O
some	O
of	O
their	O
controlling	O
genes	O
that	O
code	O
for	O
their	O
structure	O
,	O
and	O
the	O
phases	O
that	O
are	O
active	O
during	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
Some	O
of	O
the	O
most	O
important	O
ion	O
channels	O
involved	O
in	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
are	O
described	O
briefly	O
below	O
.	O
</s>
<s>
Hyperpolarization-activated	O
cyclic	O
nucleotide-gated	O
channels	O
(	O
HCN	O
channels	O
)	O
are	O
located	O
mainly	O
in	O
pacemaker	B-Algorithm
cells	I-Algorithm
,	O
these	O
channels	O
become	O
active	O
at	O
very	O
negative	O
membrane	O
potentials	O
and	O
allow	O
for	O
the	O
passage	O
of	O
both	O
Na+	O
and	O
K+	O
into	O
the	O
cell	O
(	O
which	O
is	O
a	O
movement	O
known	O
as	O
a	O
funny	B-Algorithm
current	I-Algorithm
,	O
If	O
)	O
.	O
</s>
<s>
The	O
activity	O
of	O
these	O
channels	O
in	O
the	O
SAN	O
cells	O
causes	O
the	O
membrane	O
potential	O
to	O
depolarise	O
slowly	O
and	O
so	O
they	O
are	O
thought	O
to	O
be	O
responsible	O
for	O
the	O
pacemaker	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
They	O
allow	O
for	O
a	O
rapid	O
flow	O
of	O
sodium	O
into	O
the	O
cell	O
,	O
depolarizing	O
the	O
membrane	O
completely	O
and	O
initiating	O
an	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
Due	O
to	O
the	O
rapid	O
influx	O
sodium	O
ions	O
(	O
steep	O
phase	O
0	O
in	O
action	B-Algorithm
potential	I-Algorithm
waveform	O
)	O
activation	O
and	O
inactivation	O
of	O
these	O
channels	O
happens	O
almost	O
at	O
exactly	O
the	O
same	O
time	O
.	O
</s>
<s>
This	O
influx	O
of	O
potassium	O
,	O
however	O
,	O
is	O
larger	O
when	O
the	O
membrane	O
potential	O
is	O
more	O
negative	O
than	O
the	O
equilibrium	B-Algorithm
potential	I-Algorithm
for	O
K+	O
(~-	O
90	O
mV	O
)	O
.	O
</s>
<s>
These	O
currents	O
contribute	O
to	O
the	O
early	O
repolarization	O
phase	O
(	O
phase	O
1	O
)	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
These	O
channels	O
carry	O
potassium	O
currents	O
which	O
are	O
responsible	O
for	O
the	O
plateau	O
phase	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
,	O
and	O
are	O
named	O
based	O
on	O
the	O
speed	O
at	O
which	O
they	O
activate	O
:	O
slowly	O
activating	O
IKs	O
,	O
rapidly	O
activating	O
IKr	O
and	O
ultra-rapidly	O
activating	O
IKur	O
.	O
</s>
<s>
L-type	O
channels	O
are	O
more	O
common	O
and	O
are	O
most	O
densely	O
populated	O
within	O
the	O
T-tubule	O
membrane	O
of	O
ventricular	O
cells	O
,	O
whereas	O
the	O
T-type	O
channels	O
are	O
found	O
mainly	O
within	O
atrial	O
and	O
pacemaker	B-Algorithm
cells	I-Algorithm
,	O
but	O
still	O
to	O
a	O
lesser	O
degree	O
than	O
L-type	O
channels	O
.	O
</s>
<s>
In	O
the	O
heart	B-Algorithm
's	I-Algorithm
conduction	I-Algorithm
system	I-Algorithm
electrical	O
activity	O
that	O
originates	O
from	O
the	O
sinoatrial	O
node	O
(	O
SAN	O
)	O
is	O
propagated	O
via	O
the	O
His-Purkinje	O
network	O
,	O
the	O
fastest	O
conduction	B-Algorithm
pathway	I-Algorithm
within	O
the	O
heart	O
.	O
</s>
<s>
The	O
electrical	O
signal	O
travels	O
from	O
the	O
sinoatrial	O
node	O
,	O
which	O
stimulates	O
the	O
atria	O
to	O
contract	O
,	O
to	O
the	O
atrioventricular	O
node	O
(	O
AVN	O
)	O
,	O
which	O
slows	O
down	O
conduction	B-Algorithm
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
from	O
the	O
atria	O
to	O
the	O
ventricles	O
.	O
</s>
<s>
The	O
signal	O
then	O
passes	O
down	O
through	O
a	O
bundle	O
of	O
fibres	O
called	O
the	O
bundle	B-Algorithm
of	I-Algorithm
His	I-Algorithm
,	O
located	O
between	O
the	O
ventricles	O
,	O
and	O
then	O
to	O
the	O
Purkinje	B-Algorithm
fibers	I-Algorithm
at	O
the	O
bottom	O
(	O
apex	O
)	O
of	O
the	O
heart	O
,	O
causing	O
ventricular	O
contraction	O
.	O
</s>
<s>
In	O
addition	O
to	O
the	O
SAN	O
,	O
the	O
AVN	O
and	O
Purkinje	B-Algorithm
fibres	I-Algorithm
also	O
have	O
pacemaker	O
activity	O
and	O
can	O
therefore	O
spontaneously	O
generate	O
an	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
However	O
,	O
these	O
cells	O
usually	O
do	O
not	O
depolarize	O
spontaneously	O
,	O
simply	O
because	O
action	B-Algorithm
potential	I-Algorithm
production	O
in	O
the	O
SAN	O
is	O
faster	O
.	O
</s>
<s>
This	O
means	O
that	O
before	O
the	O
AVN	O
or	O
Purkinje	B-Algorithm
fibres	I-Algorithm
reach	O
the	O
threshold	B-Algorithm
potential	I-Algorithm
for	O
an	O
action	B-Algorithm
potential	I-Algorithm
,	O
they	O
are	O
depolarized	O
by	O
the	O
oncoming	O
impulse	O
from	O
the	O
SAN	O
This	O
is	O
called	O
"	O
overdrive	O
suppression	O
"	O
.	O
</s>
<s>
Purkinje	B-Algorithm
fibres	I-Algorithm
=	O
20-40	O
beats	O
per	O
minute	O
)	O
.	O
</s>
<s>
This	O
can	O
lead	O
to	O
atrioventricular	B-Algorithm
block	I-Algorithm
,	O
where	O
the	O
signal	O
from	O
the	O
SAN	O
is	O
impaired	O
in	O
its	O
path	O
to	O
the	O
ventricles	O
.	O
</s>
<s>
The	O
speed	O
of	O
action	B-Algorithm
potential	I-Algorithm
production	O
in	O
pacemaker	B-Algorithm
cells	I-Algorithm
is	O
affected	O
,	O
but	O
not	O
controlled	O
by	O
the	O
autonomic	O
nervous	O
system	O
.	O
</s>
<s>
The	O
sympathetic	O
nervous	O
system	O
(	O
nerves	O
dominant	O
during	O
the	O
body	O
's	O
fight-or-flight	O
response	O
)	O
increase	O
heart	O
rate	O
(	O
positive	O
chronotropy	O
)	O
,	O
by	O
decreasing	O
the	O
time	O
to	O
produce	O
an	O
action	B-Algorithm
potential	I-Algorithm
in	O
the	O
SAN	O
.	O
</s>
<s>
Nerves	O
from	O
the	O
spinal	O
cord	O
release	O
a	O
molecule	O
called	O
noradrenaline	O
,	O
which	O
binds	O
to	O
and	O
activates	O
receptors	O
on	O
the	O
pacemaker	B-Algorithm
cell	I-Algorithm
membrane	O
called	O
β1	O
adrenoceptors	O
.	O
</s>
<s>
cAMP	O
binds	O
to	O
the	O
HCN	O
channels	O
(	O
see	O
above	O
)	O
,	O
increasing	O
the	O
funny	B-Algorithm
current	I-Algorithm
and	O
therefore	O
increasing	O
the	O
rate	O
of	O
depolarization	O
,	O
during	O
the	O
pacemaker	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
The	O
parasympathetic	O
nervous	O
system	O
(	O
nerves	O
dominant	O
while	O
the	O
body	O
is	O
resting	O
and	O
digesting	O
)	O
decreases	O
heart	O
rate	O
(	O
negative	O
chronotropy	O
)	O
,	O
by	O
increasing	O
the	O
time	O
taken	O
to	O
produce	O
an	O
action	B-Algorithm
potential	I-Algorithm
in	O
the	O
SAN	O
.	O
</s>
<s>
A	O
nerve	O
called	O
the	O
vagus	O
nerve	O
,	O
that	O
begins	O
in	O
the	O
brain	O
and	O
travels	O
to	O
the	O
sinoatrial	O
node	O
,	O
releases	O
a	O
molecule	O
called	O
acetylcholine	O
(	O
ACh	O
)	O
which	O
binds	O
to	O
a	O
receptor	O
located	O
on	O
the	O
outside	O
of	O
the	O
pacemaker	B-Algorithm
cell	I-Algorithm
,	O
called	O
an	O
M2	O
muscarinic	O
receptor	O
.	O
</s>
<s>
The	O
β	O
and	O
γ	O
subunits	O
activate	O
a	O
special	O
set	O
of	O
potassium	O
channels	O
,	O
increasing	O
potassium	O
flow	O
out	O
of	O
the	O
cell	O
and	O
decreasing	O
membrane	O
potential	O
,	O
meaning	O
that	O
the	O
pacemaker	B-Algorithm
cells	I-Algorithm
take	O
longer	O
to	O
reach	O
their	O
threshold	O
value	O
.	O
</s>
<s>
Antiarrhythmic	B-Algorithm
drugs	I-Algorithm
are	O
used	O
to	O
regulate	O
heart	B-Application
rhythms	I-Application
that	O
are	O
too	O
fast	O
.	O
</s>
<s>
Other	O
drugs	B-Algorithm
used	O
to	O
influence	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
include	O
sodium	O
channel	O
blockers	O
,	O
beta	O
blockers	O
,	O
potassium	O
channel	O
blockers	O
,	O
and	O
calcium	O
channel	O
blockers	O
.	O
</s>
