<s>
An	O
action	B-Algorithm
potential	I-Algorithm
occurs	O
when	O
the	O
membrane	O
potential	O
of	O
a	O
specific	O
cell	O
location	O
rapidly	O
rises	O
and	O
falls	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
occur	O
in	O
several	O
types	O
of	O
animal	O
cells	O
,	O
called	O
excitable	O
cells	O
,	O
which	O
include	O
neurons	O
,	O
muscle	O
cells	O
,	O
and	O
in	O
some	O
plant	O
cells	O
.	O
</s>
<s>
In	O
neurons	O
,	O
action	B-Algorithm
potentials	I-Algorithm
play	O
a	O
central	O
role	O
in	O
cell	O
–	O
cell	O
communication	O
by	O
providing	O
for	O
—	O
or	O
with	O
regard	O
to	O
saltatory	O
conduction	O
,	O
assisting	O
—	O
the	O
propagation	O
of	O
signals	O
along	O
the	O
neuron	O
's	O
axon	B-Algorithm
toward	O
synaptic	O
boutons	O
situated	O
at	O
the	O
ends	O
of	O
an	O
axon	B-Algorithm
;	O
these	O
signals	O
can	O
then	O
connect	O
with	O
other	O
neurons	O
at	O
synapses	B-Application
,	O
or	O
to	O
motor	O
cells	O
or	O
glands	O
.	O
</s>
<s>
In	O
muscle	O
cells	O
,	O
for	O
example	O
,	O
an	O
action	B-Algorithm
potential	I-Algorithm
is	O
the	O
first	O
step	O
in	O
the	O
chain	O
of	O
events	O
leading	O
to	O
contraction	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
in	O
neurons	O
are	O
also	O
known	O
as	O
"	O
nerve	B-Algorithm
impulses	I-Algorithm
"	O
or	O
"	O
spikes	B-Algorithm
"	O
,	O
and	O
the	O
temporal	O
sequence	O
of	O
action	B-Algorithm
potentials	I-Algorithm
generated	O
by	O
a	O
neuron	O
is	O
called	O
its	O
"	O
spike	B-Algorithm
train	I-Algorithm
"	O
.	O
</s>
<s>
A	O
neuron	O
that	O
emits	O
an	O
action	B-Algorithm
potential	I-Algorithm
,	O
or	O
nerve	B-Algorithm
impulse	I-Algorithm
,	O
is	O
often	O
said	O
to	O
"	O
fire	O
"	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
are	O
generated	O
by	O
special	O
types	O
of	O
voltage-gated	O
ion	O
channels	O
embedded	O
in	O
a	O
cell	O
's	O
plasma	O
membrane	O
.	O
</s>
<s>
After	O
an	O
action	B-Algorithm
potential	I-Algorithm
has	O
occurred	O
,	O
there	O
is	O
a	O
transient	O
negative	O
shift	O
,	O
called	O
the	O
afterhyperpolarization	O
.	O
</s>
<s>
In	O
animal	O
cells	O
,	O
there	O
are	O
two	O
primary	O
types	O
of	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
Sodium-based	O
action	B-Algorithm
potentials	I-Algorithm
usually	O
last	O
for	O
under	O
one	O
millisecond	O
,	O
but	O
calcium-based	O
action	B-Algorithm
potentials	I-Algorithm
may	O
last	O
for	O
100	O
milliseconds	O
or	O
longer	O
.	O
</s>
<s>
In	O
some	O
types	O
of	O
neurons	O
,	O
slow	O
calcium	O
spikes	B-Algorithm
provide	O
the	O
driving	O
force	O
for	O
a	O
long	O
burst	O
of	O
rapidly	O
emitted	O
sodium	O
spikes	B-Algorithm
.	O
</s>
<s>
In	O
cardiac	B-Algorithm
muscle	I-Algorithm
cells	I-Algorithm
,	O
on	O
the	O
other	O
hand	O
,	O
an	O
initial	O
fast	O
sodium	O
spike	B-Algorithm
provides	O
a	O
"	O
primer	O
"	O
to	O
provoke	O
the	O
rapid	O
onset	O
of	O
a	O
calcium	O
spike	B-Algorithm
,	O
which	O
then	O
produces	O
muscle	O
contraction	O
.	O
</s>
<s>
In	O
some	O
types	O
of	O
electrically	O
active	O
cells	O
,	O
including	O
neurons	O
and	O
muscle	O
cells	O
,	O
the	O
voltage	O
fluctuations	O
frequently	O
take	O
the	O
form	O
of	O
a	O
rapid	O
upward	O
(	O
positive	O
)	O
spike	B-Algorithm
followed	O
by	O
a	O
rapid	O
fall	O
.	O
</s>
<s>
These	O
up-and-down	O
cycles	O
are	O
known	O
as	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
In	O
muscle	O
cells	O
,	O
a	O
typical	O
action	B-Algorithm
potential	I-Algorithm
lasts	O
about	O
a	O
fifth	O
of	O
a	O
second	O
.	O
</s>
<s>
In	O
plant	O
cells	O
,	O
an	O
action	B-Algorithm
potential	I-Algorithm
may	O
last	O
three	O
seconds	O
or	O
more	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
are	O
driven	O
by	O
channel	O
proteins	O
whose	O
configuration	O
switches	O
between	O
closed	O
and	O
open	O
states	O
as	O
a	O
function	O
of	O
the	O
voltage	O
difference	O
between	O
the	O
interior	O
and	O
exterior	O
of	O
the	O
cell	O
.	O
</s>
<s>
In	O
neurons	O
,	O
the	O
types	O
of	O
ion	O
channels	O
in	O
the	O
membrane	O
usually	O
vary	O
across	O
different	O
parts	O
of	O
the	O
cell	O
,	O
giving	O
the	O
dendrites	O
,	O
axon	B-Algorithm
,	O
and	O
cell	O
body	O
different	O
electrical	O
properties	O
.	O
</s>
<s>
As	O
a	O
result	O
,	O
some	O
parts	O
of	O
the	O
membrane	O
of	O
a	O
neuron	O
may	O
be	O
excitable	O
(	O
capable	O
of	O
generating	O
action	B-Algorithm
potentials	I-Algorithm
)	O
,	O
whereas	O
others	O
are	O
not	O
.	O
</s>
<s>
Recent	O
studies	O
have	O
shown	O
that	O
the	O
most	O
excitable	O
part	O
of	O
a	O
neuron	O
is	O
the	O
part	O
after	O
the	O
axon	B-Algorithm
hillock	O
(	O
the	O
point	O
where	O
the	O
axon	B-Algorithm
leaves	O
the	O
cell	O
body	O
)	O
,	O
which	O
is	O
called	O
the	O
axonal	O
initial	O
segment	O
,	O
but	O
the	O
axon	B-Algorithm
and	O
cell	O
body	O
are	O
also	O
excitable	O
in	O
most	O
cases	O
.	O
</s>
<s>
Each	O
excitable	O
patch	O
of	O
membrane	O
has	O
two	O
important	O
levels	O
of	O
membrane	O
potential	O
:	O
the	O
resting	O
potential	O
,	O
which	O
is	O
the	O
value	O
the	O
membrane	O
potential	O
maintains	O
as	O
long	O
as	O
nothing	O
perturbs	O
the	O
cell	O
,	O
and	O
a	O
higher	O
value	O
called	O
the	O
threshold	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
At	O
the	O
axon	B-Algorithm
hillock	O
of	O
a	O
typical	O
neuron	O
,	O
the	O
resting	O
potential	O
is	O
around	O
–	O
70	O
millivolts	O
(	O
mV	O
)	O
and	O
the	O
threshold	B-Algorithm
potential	I-Algorithm
is	O
around	O
–	O
55	O
mV	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
are	O
triggered	O
when	O
enough	O
depolarization	O
accumulates	O
to	O
bring	O
the	O
membrane	O
potential	O
up	O
to	O
threshold	O
.	O
</s>
<s>
When	O
an	O
action	B-Algorithm
potential	I-Algorithm
is	O
triggered	O
,	O
the	O
membrane	O
potential	O
abruptly	O
shoots	O
upward	O
and	O
then	O
equally	O
abruptly	O
shoots	O
back	O
downward	O
,	O
often	O
ending	O
below	O
the	O
resting	O
level	O
,	O
where	O
it	O
remains	O
for	O
some	O
period	O
of	O
time	O
.	O
</s>
<s>
The	O
shape	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
is	O
stereotyped	O
;	O
this	O
means	O
that	O
the	O
rise	O
and	O
fall	O
usually	O
have	O
approximately	O
the	O
same	O
amplitude	B-Application
and	O
time	O
course	O
for	O
all	O
action	B-Algorithm
potentials	I-Algorithm
in	O
a	O
given	O
cell	O
.	O
</s>
<s>
Many	O
types	O
of	O
neurons	O
emit	O
action	B-Algorithm
potentials	I-Algorithm
constantly	O
at	O
rates	O
of	O
up	O
to	O
10	O
–	O
100	O
per	O
second	O
.	O
</s>
<s>
However	O
,	O
some	O
types	O
are	O
much	O
quieter	O
,	O
and	O
may	O
go	O
for	O
minutes	O
or	O
longer	O
without	O
emitting	O
any	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
result	O
from	O
the	O
presence	O
in	O
a	O
cell	O
's	O
membrane	O
of	O
special	O
types	O
of	O
voltage-gated	O
ion	O
channels	O
.	O
</s>
<s>
Voltage-gated	O
ion	O
channels	O
are	O
capable	O
of	O
producing	O
action	B-Algorithm
potentials	I-Algorithm
because	O
they	O
can	O
give	O
rise	O
to	O
positive	O
feedback	O
loops	O
:	O
The	O
membrane	O
potential	O
controls	O
the	O
state	O
of	O
the	O
ion	O
channels	O
,	O
but	O
the	O
state	O
of	O
the	O
ion	O
channels	O
controls	O
the	O
membrane	O
potential	O
.	O
</s>
<s>
An	O
action	B-Algorithm
potential	I-Algorithm
occurs	O
when	O
this	O
positive	O
feedback	O
cycle	O
(	O
Hodgkin	O
cycle	O
)	O
proceeds	O
explosively	O
.	O
</s>
<s>
The	O
time	O
and	O
amplitude	B-Application
trajectory	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
are	O
determined	O
by	O
the	O
biophysical	O
properties	O
of	O
the	O
voltage-gated	O
ion	O
channels	O
that	O
produce	O
it	O
.	O
</s>
<s>
Several	O
types	O
of	O
channels	O
capable	O
of	O
producing	O
the	O
positive	O
feedback	O
necessary	O
to	O
generate	O
an	O
action	B-Algorithm
potential	I-Algorithm
do	O
exist	O
.	O
</s>
<s>
Voltage-gated	O
sodium	O
channels	O
are	O
responsible	O
for	O
the	O
fast	O
action	B-Algorithm
potentials	I-Algorithm
involved	O
in	O
nerve	B-Algorithm
conduction	I-Algorithm
.	O
</s>
<s>
Slower	O
action	B-Algorithm
potentials	I-Algorithm
in	O
muscle	O
cells	O
and	O
some	O
types	O
of	O
neurons	O
are	O
generated	O
by	O
voltage-gated	O
calcium	O
channels	O
.	O
</s>
<s>
The	O
most	O
intensively	O
studied	O
type	O
of	O
voltage-dependent	O
ion	O
channels	O
comprises	O
the	O
sodium	O
channels	O
involved	O
in	O
fast	O
nerve	B-Algorithm
conduction	I-Algorithm
.	O
</s>
<s>
These	O
are	O
sometimes	O
known	O
as	O
Hodgkin-Huxley	O
sodium	O
channels	O
because	O
they	O
were	O
first	O
characterized	O
by	O
Alan	O
Hodgkin	O
and	O
Andrew	O
Huxley	O
in	O
their	O
Nobel	O
Prize-winning	O
studies	O
of	O
the	O
biophysics	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
,	O
but	O
can	O
more	O
conveniently	O
be	O
referred	O
to	O
as	O
NaV	O
channels	O
.	O
</s>
<s>
During	O
an	O
action	B-Algorithm
potential	I-Algorithm
,	O
most	O
channels	O
of	O
this	O
type	O
go	O
through	O
a	O
cycle	O
deactivated	O
→	O
activated	O
→	O
inactivated	O
→	O
deactivated	O
.	O
</s>
<s>
These	O
equations	O
have	O
been	O
extensively	O
modified	O
by	O
later	O
research	O
,	O
but	O
form	O
the	O
starting	O
point	O
for	O
most	O
theoretical	O
studies	O
of	O
action	B-Algorithm
potential	I-Algorithm
biophysics	O
.	O
</s>
<s>
The	O
sodium	O
channels	O
close	O
at	O
the	O
peak	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
,	O
while	O
potassium	O
continues	O
to	O
leave	O
the	O
cell	O
.	O
</s>
<s>
Thus	O
,	O
the	O
cell	O
fires	O
,	O
producing	O
an	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
The	O
frequency	O
at	O
which	O
a	O
neuron	O
elicits	O
action	B-Algorithm
potentials	I-Algorithm
is	O
often	O
referred	O
to	O
as	O
a	O
firing	O
rate	O
or	O
neural	B-Algorithm
firing	I-Algorithm
rate	O
.	O
</s>
<s>
Currents	O
produced	O
by	O
the	O
opening	O
of	O
voltage-gated	O
channels	O
in	O
the	O
course	O
of	O
an	O
action	B-Algorithm
potential	I-Algorithm
are	O
typically	O
significantly	O
larger	O
than	O
the	O
initial	O
stimulating	O
current	O
.	O
</s>
<s>
Thus	O
,	O
the	O
amplitude	B-Application
,	O
duration	O
,	O
and	O
shape	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
are	O
determined	O
largely	O
by	O
the	O
properties	O
of	O
the	O
excitable	O
membrane	O
and	O
not	O
the	O
amplitude	B-Application
or	O
duration	O
of	O
the	O
stimulus	O
.	O
</s>
<s>
This	O
all-or-nothing	O
property	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
sets	O
it	O
apart	O
from	O
graded	B-Algorithm
potentials	I-Algorithm
such	O
as	O
receptor	B-Algorithm
potentials	I-Algorithm
,	O
electrotonic	B-Algorithm
potentials	I-Algorithm
,	O
subthreshold	B-Algorithm
membrane	I-Algorithm
potential	I-Algorithm
oscillations	I-Algorithm
,	O
and	O
synaptic	O
potentials	O
,	O
which	O
scale	O
with	O
the	O
magnitude	O
of	O
the	O
stimulus	O
.	O
</s>
<s>
A	O
variety	O
of	O
action	B-Algorithm
potential	I-Algorithm
types	O
exist	O
in	O
many	O
cell	O
types	O
and	O
cell	O
compartments	O
as	O
determined	O
by	O
the	O
types	O
of	O
voltage-gated	O
channels	O
,	O
leak	O
channels	O
,	O
channel	O
distributions	O
,	O
ionic	O
concentrations	O
,	O
membrane	O
capacitance	O
,	O
temperature	O
,	O
and	O
other	O
factors	O
.	O
</s>
<s>
The	O
principal	O
ions	O
involved	O
in	O
an	O
action	B-Algorithm
potential	I-Algorithm
are	O
sodium	O
and	O
potassium	O
cations	O
;	O
sodium	O
ions	O
enter	O
the	O
cell	O
,	O
and	O
potassium	O
ions	O
leave	O
,	O
restoring	O
equilibrium	O
.	O
</s>
<s>
The	O
ions	O
exchanged	O
during	O
an	O
action	B-Algorithm
potential	I-Algorithm
,	O
therefore	O
,	O
make	O
a	O
negligible	O
change	O
in	O
the	O
interior	O
and	O
exterior	O
ionic	O
concentrations	O
.	O
</s>
<s>
Calcium	O
cations	O
and	O
chloride	O
anions	O
are	O
involved	O
in	O
a	O
few	O
types	O
of	O
action	B-Algorithm
potentials	I-Algorithm
,	O
such	O
as	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
and	O
the	O
action	B-Algorithm
potential	I-Algorithm
in	O
the	O
single-cell	O
alga	O
Acetabularia	O
,	O
respectively	O
.	O
</s>
<s>
Although	O
action	B-Algorithm
potentials	I-Algorithm
are	O
generated	O
locally	O
on	O
patches	O
of	O
excitable	O
membrane	O
,	O
the	O
resulting	O
currents	O
can	O
trigger	O
action	B-Algorithm
potentials	I-Algorithm
on	O
neighboring	O
stretches	O
of	O
membrane	O
,	O
precipitating	O
a	O
domino-like	O
propagation	O
.	O
</s>
<s>
In	O
contrast	O
to	O
passive	O
spread	O
of	O
electric	O
potentials	O
(	O
electrotonic	B-Algorithm
potential	I-Algorithm
)	O
,	O
action	B-Algorithm
potentials	I-Algorithm
are	O
generated	O
anew	O
along	O
excitable	O
stretches	O
of	O
membrane	O
and	O
propagate	O
without	O
decay	O
.	O
</s>
<s>
Myelinated	O
sections	O
of	O
axons	B-Algorithm
are	O
not	O
excitable	O
and	O
do	O
not	O
produce	O
action	B-Algorithm
potentials	I-Algorithm
and	O
the	O
signal	O
is	O
propagated	O
passively	O
as	O
electrotonic	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
Regularly	O
spaced	O
unmyelinated	O
patches	O
,	O
called	O
the	O
nodes	O
of	O
Ranvier	O
,	O
generate	O
action	B-Algorithm
potentials	I-Algorithm
to	O
boost	O
the	O
signal	O
.	O
</s>
<s>
Known	O
as	O
saltatory	O
conduction	O
,	O
this	O
type	O
of	O
signal	O
propagation	O
provides	O
a	O
favorable	O
tradeoff	O
of	O
signal	O
velocity	O
and	O
axon	B-Algorithm
diameter	O
.	O
</s>
<s>
Depolarization	O
of	O
axon	B-Algorithm
terminals	O
,	O
in	O
general	O
,	O
triggers	O
the	O
release	O
of	O
neurotransmitter	O
into	O
the	O
synaptic	O
cleft	O
.	O
</s>
<s>
In	O
addition	O
,	O
backpropagating	O
action	B-Algorithm
potentials	I-Algorithm
have	O
been	O
recorded	O
in	O
the	O
dendrites	O
of	O
pyramidal	O
neurons	O
,	O
which	O
are	O
ubiquitous	O
in	O
the	O
neocortex	O
.	O
</s>
<s>
These	O
are	O
thought	O
to	O
have	O
a	O
role	O
in	O
spike-timing-dependent	O
plasticity	O
.	O
</s>
<s>
In	O
the	O
Hodgkin	O
–	O
Huxley	O
membrane	O
capacitance	O
model	O
,	O
the	O
speed	O
of	O
transmission	O
of	O
an	O
action	B-Algorithm
potential	I-Algorithm
was	O
undefined	O
and	O
it	O
was	O
assumed	O
that	O
adjacent	O
areas	O
became	O
depolarized	O
due	O
to	O
released	O
ion	O
interference	O
with	O
neighbouring	O
channels	O
.	O
</s>
<s>
Alternatively	O
,	O
Gilbert	O
Ling	O
's	O
adsorption	O
hypothesis	O
,	O
posits	O
that	O
the	O
membrane	O
potential	O
and	O
action	B-Algorithm
potential	I-Algorithm
of	O
a	O
living	O
cell	O
is	O
due	O
to	O
the	O
adsorption	O
of	O
mobile	O
ions	O
onto	O
adsorption	O
sites	O
of	O
cells	O
.	O
</s>
<s>
A	O
neuron	O
's	O
ability	O
to	O
generate	O
and	O
propagate	O
an	O
action	B-Algorithm
potential	I-Algorithm
changes	O
during	O
development	O
.	O
</s>
<s>
One	O
consequence	O
of	O
the	O
decreasing	O
action	B-Algorithm
potential	I-Algorithm
duration	O
is	O
that	O
the	O
fidelity	O
of	O
the	O
signal	O
can	O
be	O
preserved	O
in	O
response	O
to	O
high	O
frequency	O
stimulation	O
.	O
</s>
<s>
In	O
the	O
early	O
development	O
of	O
many	O
organisms	O
,	O
the	O
action	B-Algorithm
potential	I-Algorithm
is	O
actually	O
initially	O
carried	O
by	O
calcium	O
current	O
rather	O
than	O
sodium	O
current	O
.	O
</s>
<s>
The	O
opening	O
and	O
closing	O
kinetics	O
of	O
calcium	O
channels	O
during	O
development	O
are	O
slower	O
than	O
those	O
of	O
the	O
voltage-gated	O
sodium	O
channels	O
that	O
will	O
carry	O
the	O
action	B-Algorithm
potential	I-Algorithm
in	O
the	O
mature	O
neurons	O
.	O
</s>
<s>
The	O
longer	O
opening	O
times	O
for	O
the	O
calcium	O
channels	O
can	O
lead	O
to	O
action	B-Algorithm
potentials	I-Algorithm
that	O
are	O
considerably	O
slower	O
than	O
those	O
of	O
mature	O
neurons	O
.	O
</s>
<s>
Xenopus	O
neurons	O
initially	O
have	O
action	B-Algorithm
potentials	I-Algorithm
that	O
take	O
60	O
–	O
90	O
ms.	O
During	O
development	O
,	O
this	O
time	O
decreases	O
to	O
1	O
ms.	O
</s>
<s>
In	O
order	O
for	O
the	O
transition	O
from	O
a	O
calcium-dependent	O
action	B-Algorithm
potential	I-Algorithm
to	O
a	O
sodium-dependent	O
action	B-Algorithm
potential	I-Algorithm
to	O
proceed	O
new	O
channels	O
must	O
be	O
added	O
to	O
the	O
membrane	O
.	O
</s>
<s>
If	O
action	B-Algorithm
potentials	I-Algorithm
in	O
Xenopus	O
myocytes	O
are	O
blocked	O
,	O
the	O
typical	O
increase	O
in	O
sodium	O
and	O
potassium	O
current	O
density	O
is	O
prevented	O
or	O
delayed	O
.	O
</s>
<s>
Several	O
types	O
of	O
cells	O
support	O
an	O
action	B-Algorithm
potential	I-Algorithm
,	O
such	O
as	O
plant	O
cells	O
,	O
muscle	O
cells	O
,	O
and	O
the	O
specialized	O
cells	O
of	O
the	O
heart	O
(	O
in	O
which	O
occurs	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
)	O
.	O
</s>
<s>
However	O
,	O
the	O
main	O
excitable	O
cell	O
is	O
the	O
neuron	O
,	O
which	O
also	O
has	O
the	O
simplest	O
mechanism	O
for	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
Neurons	O
are	O
electrically	O
excitable	O
cells	O
composed	O
,	O
in	O
general	O
,	O
of	O
one	O
or	O
more	O
dendrites	O
,	O
a	O
single	O
soma	O
,	O
a	O
single	O
axon	B-Algorithm
and	O
one	O
or	O
more	O
axon	B-Algorithm
terminals	O
.	O
</s>
<s>
Their	O
protrusions	O
,	O
known	O
as	O
dendritic	O
spines	O
,	O
are	O
designed	O
to	O
capture	O
the	O
neurotransmitters	O
released	O
by	O
the	O
presynaptic	B-Application
neuron	O
.	O
</s>
<s>
Emerging	O
out	O
from	O
the	O
soma	O
is	O
the	O
axon	B-Algorithm
hillock	O
.	O
</s>
<s>
In	O
general	O
,	O
it	O
is	O
considered	O
to	O
be	O
the	O
spike	B-Algorithm
initiation	O
zone	O
for	O
action	B-Algorithm
potentials	I-Algorithm
,	O
i.e.	O
</s>
<s>
Immediately	O
after	O
the	O
axon	B-Algorithm
hillock	O
is	O
the	O
axon	B-Algorithm
.	O
</s>
<s>
The	O
axon	B-Algorithm
is	O
insulated	O
by	O
a	O
myelin	O
sheath	O
.	O
</s>
<s>
To	O
be	O
specific	O
,	O
myelin	O
wraps	O
multiple	O
times	O
around	O
the	O
axonal	O
segment	O
,	O
forming	O
a	O
thick	O
fatty	O
layer	O
that	O
prevents	O
ions	O
from	O
entering	O
or	O
escaping	O
the	O
axon	B-Algorithm
.	O
</s>
<s>
This	O
insulation	O
,	O
however	O
,	O
has	O
the	O
restriction	O
that	O
no	O
channels	O
can	O
be	O
present	O
on	O
the	O
surface	O
of	O
the	O
axon	B-Algorithm
.	O
</s>
<s>
These	O
nodes	O
of	O
Ranvier	O
can	O
be	O
considered	O
to	O
be	O
"	O
mini	O
axon	B-Algorithm
hillocks	O
"	O
,	O
as	O
their	O
purpose	O
is	O
to	O
boost	O
the	O
signal	O
in	O
order	O
to	O
prevent	O
significant	O
signal	O
decay	O
.	O
</s>
<s>
At	O
the	O
furthest	O
end	O
,	O
the	O
axon	B-Algorithm
loses	O
its	O
insulation	O
and	O
begins	O
to	O
branch	O
into	O
several	O
axon	B-Algorithm
terminals	O
.	O
</s>
<s>
These	O
presynaptic	B-Application
terminals	O
,	O
or	O
synaptic	O
boutons	O
,	O
are	O
a	O
specialized	O
area	O
within	O
the	O
axon	B-Algorithm
of	O
the	O
presynaptic	B-Application
cell	O
that	O
contains	O
neurotransmitters	O
enclosed	O
in	O
small	O
membrane-bound	O
spheres	O
called	O
synaptic	O
vesicles	O
.	O
</s>
<s>
Before	O
considering	O
the	O
propagation	O
of	O
action	B-Algorithm
potentials	I-Algorithm
along	O
axons	B-Algorithm
and	O
their	O
termination	O
at	O
the	O
synaptic	O
knobs	O
,	O
it	O
is	O
helpful	O
to	O
consider	O
the	O
methods	O
by	O
which	O
action	B-Algorithm
potentials	I-Algorithm
can	O
be	O
initiated	O
at	O
the	O
axon	B-Algorithm
hillock	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
are	O
most	O
commonly	O
initiated	O
by	O
excitatory	O
postsynaptic	O
potentials	O
from	O
a	O
presynaptic	B-Application
neuron	O
.	O
</s>
<s>
Typically	O
,	O
neurotransmitter	O
molecules	O
are	O
released	O
by	O
the	O
presynaptic	B-Application
neuron	O
.	O
</s>
<s>
If	O
the	O
binding	O
increases	O
the	O
voltage	O
(	O
depolarizes	O
the	O
membrane	O
)	O
,	O
the	O
synapse	B-Application
is	O
excitatory	O
.	O
</s>
<s>
Typically	O
,	O
the	O
voltage	O
stimulus	O
decays	O
exponentially	O
with	O
the	O
distance	O
from	O
the	O
synapse	B-Application
and	O
with	O
time	O
from	O
the	O
binding	O
of	O
the	O
neurotransmitter	O
.	O
</s>
<s>
Some	O
fraction	O
of	O
an	O
excitatory	O
voltage	O
may	O
reach	O
the	O
axon	B-Algorithm
hillock	O
and	O
may	O
(	O
in	O
rare	O
cases	O
)	O
depolarize	O
the	O
membrane	O
enough	O
to	O
provoke	O
a	O
new	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
More	O
typically	O
,	O
the	O
excitatory	O
potentials	O
from	O
several	O
synapses	B-Application
must	O
work	O
together	O
at	O
nearly	O
the	O
same	O
time	O
to	O
provoke	O
a	O
new	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
Neurotransmission	O
can	O
also	O
occur	O
through	O
electrical	O
synapses	B-Application
.	O
</s>
<s>
Due	O
to	O
the	O
direct	O
connection	O
between	O
excitable	O
cells	O
in	O
the	O
form	O
of	O
gap	O
junctions	O
,	O
an	O
action	B-Algorithm
potential	I-Algorithm
can	O
be	O
transmitted	O
directly	O
from	O
one	O
cell	O
to	O
the	O
next	O
in	O
either	O
direction	O
.	O
</s>
<s>
Rectifying	O
channels	O
ensure	O
that	O
action	B-Algorithm
potentials	I-Algorithm
move	O
only	O
in	O
one	O
direction	O
through	O
an	O
electrical	O
synapse	B-Application
.	O
</s>
<s>
Electrical	O
synapses	B-Application
are	O
found	O
in	O
all	O
nervous	O
systems	O
,	O
including	O
the	O
human	O
brain	O
,	O
although	O
they	O
are	O
a	O
distinct	O
minority	O
.	O
</s>
<s>
The	O
amplitude	B-Application
of	O
an	O
action	B-Algorithm
potential	I-Algorithm
is	O
often	O
thought	O
to	O
be	O
independent	O
of	O
the	O
amount	O
of	O
current	O
that	O
produced	O
it	O
.	O
</s>
<s>
In	O
other	O
words	O
,	O
larger	O
currents	O
do	O
not	O
create	O
larger	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
Therefore	O
,	O
action	B-Algorithm
potentials	I-Algorithm
are	O
said	O
to	O
be	O
all-or-none	O
signals	O
,	O
since	O
either	O
they	O
occur	O
fully	O
or	O
they	O
do	O
not	O
occur	O
at	O
all	O
.	O
</s>
<s>
This	O
is	O
in	O
contrast	O
to	O
receptor	B-Algorithm
potentials	I-Algorithm
,	O
whose	O
amplitudes	B-Application
are	O
dependent	O
on	O
the	O
intensity	O
of	O
a	O
stimulus	O
.	O
</s>
<s>
In	O
both	O
cases	O
,	O
the	O
frequency	O
of	O
action	B-Algorithm
potentials	I-Algorithm
is	O
correlated	O
with	O
the	O
intensity	O
of	O
a	O
stimulus	O
.	O
</s>
<s>
Despite	O
the	O
classical	O
view	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
as	O
a	O
stereotyped	O
,	O
uniform	O
signal	O
having	O
dominated	O
the	O
field	O
of	O
neuroscience	O
for	O
many	O
decades	O
,	O
newer	O
evidence	O
does	O
suggest	O
that	O
action	B-Algorithm
potentials	I-Algorithm
are	O
more	O
complex	O
events	O
indeed	O
capable	O
of	O
transmitting	O
information	O
through	O
not	O
just	O
their	O
amplitude	B-Application
,	O
but	O
their	O
duration	O
and	O
phase	O
as	O
well	O
,	O
sometimes	O
even	O
up	O
to	O
distances	O
originally	O
not	O
thought	O
to	O
be	O
possible	O
.	O
</s>
<s>
In	O
sensory	B-Architecture
neurons	I-Architecture
,	O
an	O
external	O
signal	O
such	O
as	O
pressure	O
,	O
temperature	O
,	O
light	O
,	O
or	O
sound	O
is	O
coupled	O
with	O
the	O
opening	O
and	O
closing	O
of	O
ion	O
channels	O
,	O
which	O
in	O
turn	O
alter	O
the	O
ionic	O
permeabilities	O
of	O
the	O
membrane	O
and	O
its	O
voltage	O
.	O
</s>
<s>
These	O
voltage	O
changes	O
can	O
again	O
be	O
excitatory	O
(	O
depolarizing	O
)	O
or	O
inhibitory	O
(	O
hyperpolarizing	O
)	O
and	O
,	O
in	O
some	O
sensory	B-Architecture
neurons	I-Architecture
,	O
their	O
combined	O
effects	O
can	O
depolarize	O
the	O
axon	B-Algorithm
hillock	O
enough	O
to	O
provoke	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
Some	O
examples	O
in	O
humans	O
include	O
the	O
olfactory	O
receptor	O
neuron	O
and	O
Meissner	B-Algorithm
's	I-Algorithm
corpuscle	I-Algorithm
,	O
which	O
are	O
critical	O
for	O
the	O
sense	O
of	O
smell	O
and	O
touch	O
,	O
respectively	O
.	O
</s>
<s>
However	O
,	O
not	O
all	O
sensory	B-Architecture
neurons	I-Architecture
convert	O
their	O
external	O
signals	O
into	O
action	B-Algorithm
potentials	I-Algorithm
;	O
some	O
do	O
not	O
even	O
have	O
an	O
axon	B-Algorithm
.	O
</s>
<s>
Instead	O
,	O
they	O
may	O
convert	O
the	O
signal	O
into	O
the	O
release	O
of	O
a	O
neurotransmitter	O
,	O
or	O
into	O
continuous	O
graded	B-Algorithm
potentials	I-Algorithm
,	O
either	O
of	O
which	O
may	O
stimulate	O
subsequent	O
neuron(s )	O
into	O
firing	O
an	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
In	O
similar	O
manner	O
,	O
in	O
the	O
human	O
retina	O
,	O
the	O
initial	O
photoreceptor	O
cells	O
and	O
the	O
next	O
layer	O
of	O
cells	O
(	O
comprising	O
bipolar	O
cells	O
and	O
horizontal	O
cells	O
)	O
do	O
not	O
produce	O
action	B-Algorithm
potentials	I-Algorithm
;	O
only	O
some	O
amacrine	O
cells	O
and	O
the	O
third	O
layer	O
,	O
the	O
ganglion	O
cells	O
,	O
produce	O
action	B-Algorithm
potentials	I-Algorithm
,	O
which	O
then	O
travel	O
up	O
the	O
optic	B-Application
nerve	I-Application
.	O
</s>
<s>
In	O
sensory	B-Architecture
neurons	I-Architecture
,	O
action	B-Algorithm
potentials	I-Algorithm
result	O
from	O
an	O
external	O
stimulus	O
.	O
</s>
<s>
However	O
,	O
some	O
excitable	O
cells	O
require	O
no	O
such	O
stimulus	O
to	O
fire	O
:	O
They	O
spontaneously	O
depolarize	O
their	O
axon	B-Algorithm
hillock	O
and	O
fire	O
action	B-Algorithm
potentials	I-Algorithm
at	O
a	O
regular	O
rate	O
,	O
like	O
an	O
internal	O
clock	O
.	O
</s>
<s>
The	O
voltage	O
traces	O
of	O
such	O
cells	O
are	O
known	O
as	O
pacemaker	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
The	O
cardiac	B-Algorithm
pacemaker	I-Algorithm
cells	I-Algorithm
of	O
the	O
sinoatrial	O
node	O
in	O
the	O
heart	O
provide	O
a	O
good	O
example	O
.	O
</s>
<s>
Although	O
such	O
pacemaker	B-Algorithm
potentials	I-Algorithm
have	O
a	O
natural	B-Algorithm
rhythm	I-Algorithm
,	O
it	O
can	O
be	O
adjusted	O
by	O
external	O
stimuli	O
;	O
for	O
instance	O
,	O
heart	O
rate	O
can	O
be	O
altered	O
by	O
pharmaceuticals	O
as	O
well	O
as	O
signals	O
from	O
the	O
sympathetic	O
and	O
parasympathetic	O
nerves	O
.	O
</s>
<s>
In	O
some	O
cases	O
,	O
the	O
regulation	O
of	O
frequency	O
can	O
be	O
more	O
complex	O
,	O
leading	O
to	O
patterns	O
of	O
action	B-Algorithm
potentials	I-Algorithm
,	O
such	O
as	O
bursting	B-Algorithm
.	O
</s>
<s>
The	O
course	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
can	O
be	O
divided	O
into	O
five	O
parts	O
:	O
the	O
rising	O
phase	O
,	O
the	O
peak	O
phase	O
,	O
the	O
falling	O
phase	O
,	O
the	O
undershoot	O
phase	O
,	O
and	O
the	O
refractory	O
period	O
.	O
</s>
<s>
Finally	O
,	O
the	O
time	O
during	O
which	O
a	O
subsequent	O
action	B-Algorithm
potential	I-Algorithm
is	O
impossible	O
or	O
difficult	O
to	O
fire	O
is	O
called	O
the	O
refractory	O
period	O
,	O
which	O
may	O
overlap	O
with	O
the	O
other	O
phases	O
.	O
</s>
<s>
The	O
course	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
is	O
determined	O
by	O
two	O
coupled	O
effects	O
.	O
</s>
<s>
This	O
sets	O
up	O
the	O
possibility	O
for	O
positive	O
feedback	O
,	O
which	O
is	O
a	O
key	O
part	O
of	O
the	O
rising	O
phase	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
The	O
voltages	O
and	O
currents	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
in	O
all	O
of	O
its	O
phases	O
were	O
modeled	O
accurately	O
by	O
Alan	O
Lloyd	O
Hodgkin	O
and	O
Andrew	O
Huxley	O
in	O
1952	O
,	O
for	O
which	O
they	O
were	O
awarded	O
the	O
Nobel	O
Prize	O
in	O
Physiology	O
or	O
Medicine	O
in	O
1963	O
.	O
</s>
<s>
A	O
typical	O
action	B-Algorithm
potential	I-Algorithm
begins	O
at	O
the	O
axon	B-Algorithm
hillock	O
with	O
a	O
sufficiently	O
strong	O
depolarization	O
,	O
e.g.	O
,	O
a	O
stimulus	O
that	O
increases	O
Vm	O
.	O
</s>
<s>
This	O
depolarization	O
is	O
often	O
caused	O
by	O
the	O
injection	O
of	O
extra	O
sodium	O
cations	O
into	O
the	O
cell	O
;	O
these	O
cations	O
can	O
come	O
from	O
a	O
wide	O
variety	O
of	O
sources	O
,	O
such	O
as	O
chemical	O
synapses	B-Application
,	O
sensory	B-Architecture
neurons	I-Architecture
or	O
pacemaker	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
Depolarization	O
opens	O
both	O
the	O
sodium	O
and	O
potassium	O
channels	O
in	O
the	O
membrane	O
,	O
allowing	O
the	O
ions	O
to	O
flow	O
into	O
and	O
out	O
of	O
the	O
axon	B-Algorithm
,	O
respectively	O
.	O
</s>
<s>
The	O
sharp	O
rise	O
in	O
Vm	O
and	O
sodium	O
permeability	O
correspond	O
to	O
the	O
rising	O
phase	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
The	O
critical	O
threshold	O
voltage	O
for	O
this	O
runaway	O
condition	O
is	O
usually	O
around	O
−45mV	O
,	O
but	O
it	O
depends	O
on	O
the	O
recent	O
activity	O
of	O
the	O
axon	B-Algorithm
.	O
</s>
<s>
A	O
cell	O
that	O
has	O
just	O
fired	O
an	O
action	B-Algorithm
potential	I-Algorithm
cannot	O
fire	O
another	O
one	O
immediately	O
,	O
since	O
the	O
Na+	O
channels	O
have	O
not	O
recovered	O
from	O
the	O
inactivated	O
state	O
.	O
</s>
<s>
The	O
period	O
during	O
which	O
no	O
new	O
action	B-Algorithm
potential	I-Algorithm
can	O
be	O
fired	O
is	O
called	O
the	O
absolute	O
refractory	O
period	O
.	O
</s>
<s>
At	O
longer	O
times	O
,	O
after	O
some	O
but	O
not	O
all	O
of	O
the	O
ion	O
channels	O
have	O
recovered	O
,	O
the	O
axon	B-Algorithm
can	O
be	O
stimulated	O
to	O
produce	O
another	O
action	B-Algorithm
potential	I-Algorithm
,	O
but	O
with	O
a	O
higher	O
threshold	O
,	O
requiring	O
a	O
much	O
stronger	O
depolarization	O
,	O
e.g.	O
,	O
to	O
−30mV	O
.	O
</s>
<s>
The	O
period	O
during	O
which	O
action	B-Algorithm
potentials	I-Algorithm
are	O
unusually	O
difficult	O
to	O
evoke	O
is	O
called	O
the	O
relative	O
refractory	O
period	O
.	O
</s>
<s>
At	O
the	O
peak	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
,	O
the	O
sodium	O
permeability	O
is	O
maximized	O
and	O
the	O
membrane	O
voltage	O
Vm	O
is	O
nearly	O
equal	O
to	O
the	O
sodium	O
equilibrium	O
voltage	O
ENa	O
.	O
</s>
<s>
Combined	O
,	O
these	O
changes	O
in	O
sodium	O
and	O
potassium	O
permeability	O
cause	O
Vm	O
to	O
drop	O
quickly	O
,	O
repolarizing	O
the	O
membrane	O
and	O
producing	O
the	O
"	O
falling	O
phase	O
"	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
In	O
addition	O
,	O
further	O
potassium	O
channels	O
open	O
in	O
response	O
to	O
the	O
influx	O
of	O
calcium	O
ions	O
during	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
Each	O
action	B-Algorithm
potential	I-Algorithm
is	O
followed	O
by	O
a	O
refractory	O
period	O
,	O
which	O
can	O
be	O
divided	O
into	O
an	O
absolute	O
refractory	O
period	O
,	O
during	O
which	O
it	O
is	O
impossible	O
to	O
evoke	O
another	O
action	B-Algorithm
potential	I-Algorithm
,	O
and	O
then	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
.	O
</s>
<s>
When	O
closing	O
after	O
an	O
action	B-Algorithm
potential	I-Algorithm
,	O
sodium	O
channels	O
enter	O
an	O
"	O
inactivated	O
"	O
state	O
,	O
in	O
which	O
they	O
cannot	O
be	O
made	O
to	O
open	O
regardless	O
of	O
the	O
membrane	O
potential	O
—	O
this	O
gives	O
rise	O
to	O
the	O
absolute	O
refractory	O
period	O
.	O
</s>
<s>
The	O
absolute	O
refractory	O
period	O
is	O
largely	O
responsible	O
for	O
the	O
unidirectional	O
propagation	O
of	O
action	B-Algorithm
potentials	I-Algorithm
along	O
axons	B-Algorithm
.	O
</s>
<s>
At	O
any	O
given	O
moment	O
,	O
the	O
patch	O
of	O
axon	B-Algorithm
behind	O
the	O
actively	O
spiking	O
part	O
is	O
refractory	O
,	O
but	O
the	O
patch	O
in	O
front	O
,	O
not	O
having	O
been	O
activated	O
recently	O
,	O
is	O
capable	O
of	O
being	O
stimulated	O
by	O
the	O
depolarization	O
from	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
The	O
action	B-Algorithm
potential	I-Algorithm
generated	O
at	O
the	O
axon	B-Algorithm
hillock	O
propagates	O
as	O
a	O
wave	O
along	O
the	O
axon	B-Algorithm
.	O
</s>
<s>
The	O
currents	O
flowing	O
inwards	O
at	O
a	O
point	O
on	O
the	O
axon	B-Algorithm
during	O
an	O
action	B-Algorithm
potential	I-Algorithm
spread	O
out	O
along	O
the	O
axon	B-Algorithm
,	O
and	O
depolarize	O
the	O
adjacent	O
sections	O
of	O
its	O
membrane	O
.	O
</s>
<s>
If	O
sufficiently	O
strong	O
,	O
this	O
depolarization	O
provokes	O
a	O
similar	O
action	B-Algorithm
potential	I-Algorithm
at	O
the	O
neighboring	O
membrane	O
patches	O
.	O
</s>
<s>
After	O
crushing	O
or	O
cooling	O
nerve	O
segments	O
and	O
thus	O
blocking	O
the	O
action	B-Algorithm
potentials	I-Algorithm
,	O
he	O
showed	O
that	O
an	O
action	B-Algorithm
potential	I-Algorithm
arriving	O
on	O
one	O
side	O
of	O
the	O
block	O
could	O
provoke	O
another	O
action	B-Algorithm
potential	I-Algorithm
on	O
the	O
other	O
,	O
provided	O
that	O
the	O
blocked	O
segment	O
was	O
sufficiently	O
short	O
.	O
</s>
<s>
Once	O
an	O
action	B-Algorithm
potential	I-Algorithm
has	O
occurred	O
at	O
a	O
patch	O
of	O
membrane	O
,	O
the	O
membrane	O
patch	O
needs	O
time	O
to	O
recover	O
before	O
it	O
can	O
fire	O
again	O
.	O
</s>
<s>
Although	O
it	O
limits	O
the	O
frequency	O
of	O
firing	O
,	O
the	O
absolute	O
refractory	O
period	O
ensures	O
that	O
the	O
action	B-Algorithm
potential	I-Algorithm
moves	O
in	O
only	O
one	O
direction	O
along	O
an	O
axon	B-Algorithm
.	O
</s>
<s>
The	O
currents	O
flowing	O
in	O
due	O
to	O
an	O
action	B-Algorithm
potential	I-Algorithm
spread	O
out	O
in	O
both	O
directions	O
along	O
the	O
axon	B-Algorithm
.	O
</s>
<s>
However	O
,	O
only	O
the	O
unfired	O
part	O
of	O
the	O
axon	B-Algorithm
can	O
respond	O
with	O
an	O
action	B-Algorithm
potential	I-Algorithm
;	O
the	O
part	O
that	O
has	O
just	O
fired	O
is	O
unresponsive	O
until	O
the	O
action	B-Algorithm
potential	I-Algorithm
is	O
safely	O
out	O
of	O
range	O
and	O
cannot	O
restimulate	O
that	O
part	O
.	O
</s>
<s>
In	O
the	O
usual	O
orthodromic	O
conduction	O
,	O
the	O
action	B-Algorithm
potential	I-Algorithm
propagates	O
from	O
the	O
axon	B-Algorithm
hillock	O
towards	O
the	O
synaptic	O
knobs	O
(	O
the	O
axonal	O
termini	O
)	O
;	O
propagation	O
in	O
the	O
opposite	O
direction	O
—	O
known	O
as	O
antidromic	O
conduction	O
—	O
is	O
very	O
rare	O
.	O
</s>
<s>
However	O
,	O
if	O
a	O
laboratory	O
axon	B-Algorithm
is	O
stimulated	O
in	O
its	O
middle	O
,	O
both	O
halves	O
of	O
the	O
axon	B-Algorithm
are	O
"	O
fresh	O
"	O
,	O
i.e.	O
,	O
unfired	O
;	O
then	O
two	O
action	B-Algorithm
potentials	I-Algorithm
will	O
be	O
generated	O
,	O
one	O
traveling	O
towards	O
the	O
axon	B-Algorithm
hillock	O
and	O
the	O
other	O
traveling	O
towards	O
the	O
synaptic	O
knobs	O
.	O
</s>
<s>
In	O
order	O
to	O
enable	O
fast	O
and	O
efficient	O
transduction	O
of	O
electrical	O
signals	O
in	O
the	O
nervous	O
system	O
,	O
certain	O
neuronal	O
axons	B-Algorithm
are	O
covered	O
with	O
myelin	O
sheaths	O
.	O
</s>
<s>
Myelin	O
is	O
a	O
multilamellar	O
membrane	O
that	O
enwraps	O
the	O
axon	B-Algorithm
in	O
segments	O
separated	O
by	O
intervals	O
known	O
as	O
nodes	O
of	O
Ranvier	O
.	O
</s>
<s>
Myelin	O
sheath	O
reduces	O
membrane	O
capacitance	O
and	O
increases	O
membrane	O
resistance	O
in	O
the	O
inter-node	O
intervals	O
,	O
thus	O
allowing	O
a	O
fast	O
,	O
saltatory	O
movement	O
of	O
action	B-Algorithm
potentials	I-Algorithm
from	O
node	O
to	O
node	O
.	O
</s>
<s>
Not	O
all	O
neurons	O
in	O
vertebrates	O
are	O
myelinated	O
;	O
for	O
example	O
,	O
axons	B-Algorithm
of	O
the	O
neurons	O
comprising	O
the	O
autonomous	O
nervous	O
system	O
are	O
not	O
,	O
in	O
general	O
,	O
myelinated	O
.	O
</s>
<s>
Myelin	O
prevents	O
ions	O
from	O
entering	O
or	O
leaving	O
the	O
axon	B-Algorithm
along	O
myelinated	O
segments	O
.	O
</s>
<s>
As	O
a	O
general	O
rule	O
,	O
myelination	O
increases	O
the	O
conduction	O
velocity	O
of	O
action	B-Algorithm
potentials	I-Algorithm
and	O
makes	O
them	O
more	O
energy-efficient	O
.	O
</s>
<s>
Whether	O
saltatory	O
or	O
not	O
,	O
the	O
mean	O
conduction	O
velocity	O
of	O
an	O
action	B-Algorithm
potential	I-Algorithm
ranges	O
from	O
1meter	O
per	O
second	O
(	O
m/s	O
)	O
to	O
over	O
100m/s	O
,	O
and	O
,	O
in	O
general	O
,	O
increases	O
with	O
axonal	O
diameter	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
cannot	O
propagate	O
through	O
the	O
membrane	O
in	O
myelinated	O
segments	O
of	O
the	O
axon	B-Algorithm
.	O
</s>
<s>
Instead	O
,	O
the	O
ionic	O
current	O
from	O
an	O
action	B-Algorithm
potential	I-Algorithm
at	O
one	O
node	O
of	O
Ranvier	O
provokes	O
another	O
action	B-Algorithm
potential	I-Algorithm
at	O
the	O
next	O
node	O
;	O
this	O
apparent	O
"	O
hopping	O
"	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
from	O
node	O
to	O
node	O
is	O
known	O
as	O
saltatory	O
conduction	O
.	O
</s>
<s>
By	O
contrast	O
,	O
in	O
unmyelinated	O
axons	B-Algorithm
,	O
the	O
action	B-Algorithm
potential	I-Algorithm
provokes	O
another	O
in	O
the	O
membrane	O
immediately	O
adjacent	O
,	O
and	O
moves	O
continuously	O
down	O
the	O
axon	B-Algorithm
like	O
a	O
wave	O
.	O
</s>
<s>
For	O
axons	B-Algorithm
larger	O
than	O
a	O
minimum	O
diameter	O
(	O
roughly	O
1	O
micrometre	O
)	O
,	O
myelination	O
increases	O
the	O
conduction	O
velocity	O
of	O
an	O
action	B-Algorithm
potential	I-Algorithm
,	O
typically	O
tenfold	O
.	O
</s>
<s>
For	O
example	O
,	O
action	B-Algorithm
potentials	I-Algorithm
move	O
at	O
roughly	O
the	O
same	O
speed	O
(	O
25m/s	O
)	O
in	O
a	O
myelinated	O
frog	B-Algorithm
axon	B-Algorithm
and	O
an	O
unmyelinated	O
squid	B-Protocol
giant	O
axon	B-Algorithm
,	O
but	O
the	O
frog	B-Algorithm
axon	B-Algorithm
has	O
a	O
roughly	O
30-fold	O
smaller	O
diameter	O
and	O
1000-fold	O
smaller	O
cross-sectional	O
area	O
.	O
</s>
<s>
This	O
saving	O
is	O
a	O
significant	O
selective	B-Application
advantage	I-Application
,	O
since	O
the	O
human	O
nervous	O
system	O
uses	O
approximately	O
20%	O
of	O
the	O
body	O
's	O
metabolic	O
energy	O
.	O
</s>
<s>
The	O
length	O
of	O
axons	B-Algorithm
 '	O
myelinated	O
segments	O
is	O
important	O
to	O
the	O
success	O
of	O
saltatory	O
conduction	O
.	O
</s>
<s>
They	O
should	O
be	O
as	O
long	O
as	O
possible	O
to	O
maximize	O
the	O
speed	O
of	O
conduction	O
,	O
but	O
not	O
so	O
long	O
that	O
the	O
arriving	O
signal	O
is	O
too	O
weak	O
to	O
provoke	O
an	O
action	B-Algorithm
potential	I-Algorithm
at	O
the	O
next	O
node	O
of	O
Ranvier	O
.	O
</s>
<s>
In	O
nature	O
,	O
myelinated	O
segments	O
are	O
generally	O
long	O
enough	O
for	O
the	O
passively	O
propagated	O
signal	O
to	O
travel	O
for	O
at	O
least	O
two	O
nodes	O
while	O
retaining	O
enough	O
amplitude	B-Application
to	O
fire	O
an	O
action	B-Algorithm
potential	I-Algorithm
at	O
the	O
second	O
or	O
third	O
node	O
.	O
</s>
<s>
However	O
,	O
action	B-Algorithm
potentials	I-Algorithm
may	O
end	O
prematurely	O
in	O
certain	O
places	O
where	O
the	O
safety	O
factor	O
is	O
low	O
,	O
even	O
in	O
unmyelinated	O
neurons	O
;	O
a	O
common	O
example	O
is	O
the	O
branch	O
point	O
of	O
an	O
axon	B-Algorithm
,	O
where	O
it	O
divides	O
into	O
two	O
axons	B-Algorithm
.	O
</s>
<s>
Some	O
diseases	O
degrade	O
myelin	O
and	O
impair	O
saltatory	O
conduction	O
,	O
reducing	O
the	O
conduction	O
velocity	O
of	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
The	O
flow	O
of	O
currents	O
within	O
an	O
axon	B-Algorithm
can	O
be	O
described	O
quantitatively	O
by	O
cable	O
theory	O
and	O
its	O
elaborations	O
,	O
such	O
as	O
the	O
compartmental	O
model	O
.	O
</s>
<s>
In	O
a	O
similar	O
manner	O
,	O
if	O
the	O
internal	O
resistance	O
per	O
unit	O
length	O
ri	O
is	O
lower	O
in	O
one	O
axon	B-Algorithm
than	O
in	O
another	O
(	O
e.g.	O
,	O
because	O
the	O
radius	O
of	O
the	O
former	O
is	O
larger	O
)	O
,	O
the	O
spatial	O
decay	O
length	O
λ	O
becomes	O
longer	O
and	O
the	O
conduction	O
velocity	O
of	O
an	O
action	B-Algorithm
potential	I-Algorithm
should	O
increase	O
.	O
</s>
<s>
In	O
general	O
,	O
action	B-Algorithm
potentials	I-Algorithm
that	O
reach	O
the	O
synaptic	O
knobs	O
cause	O
a	O
neurotransmitter	O
to	O
be	O
released	O
into	O
the	O
synaptic	O
cleft	O
.	O
</s>
<s>
Neurotransmitters	O
are	O
small	O
molecules	O
that	O
may	O
open	O
ion	O
channels	O
in	O
the	O
postsynaptic	O
cell	O
;	O
most	O
axons	B-Algorithm
have	O
the	O
same	O
neurotransmitter	O
at	O
all	O
of	O
their	O
termini	O
.	O
</s>
<s>
The	O
arrival	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
opens	O
voltage-sensitive	O
calcium	O
channels	O
in	O
the	O
presynaptic	B-Application
membrane	O
;	O
the	O
influx	O
of	O
calcium	O
causes	O
vesicles	O
filled	O
with	O
neurotransmitter	O
to	O
migrate	O
to	O
the	O
cell	O
's	O
surface	O
and	O
release	O
their	O
contents	O
into	O
the	O
synaptic	O
cleft	O
.	O
</s>
<s>
Some	O
synapses	B-Application
dispense	O
with	O
the	O
"	O
middleman	O
"	O
of	O
the	O
neurotransmitter	O
,	O
and	O
connect	O
the	O
presynaptic	B-Application
and	O
postsynaptic	O
cells	O
together	O
.	O
</s>
<s>
When	O
an	O
action	B-Algorithm
potential	I-Algorithm
reaches	O
such	O
a	O
synapse	B-Application
,	O
the	O
ionic	O
currents	O
flowing	O
into	O
the	O
presynaptic	B-Application
cell	O
can	O
cross	O
the	O
barrier	O
of	O
the	O
two	O
cell	O
membranes	O
and	O
enter	O
the	O
postsynaptic	O
cell	O
through	O
pores	O
known	O
as	O
connexons	O
.	O
</s>
<s>
Thus	O
,	O
the	O
ionic	O
currents	O
of	O
the	O
presynaptic	B-Application
action	B-Algorithm
potential	I-Algorithm
can	O
directly	O
stimulate	O
the	O
postsynaptic	O
cell	O
.	O
</s>
<s>
Electrical	O
synapses	B-Application
allow	O
for	O
faster	O
transmission	O
because	O
they	O
do	O
not	O
require	O
the	O
slow	O
diffusion	O
of	O
neurotransmitters	O
across	O
the	O
synaptic	O
cleft	O
.	O
</s>
<s>
Hence	O
,	O
electrical	O
synapses	B-Application
are	O
used	O
whenever	O
fast	O
response	O
and	O
coordination	O
of	O
timing	O
are	O
crucial	O
,	O
as	O
in	O
escape	O
reflexes	B-Algorithm
,	O
the	O
retina	O
of	O
vertebrates	O
,	O
and	O
the	O
heart	O
.	O
</s>
<s>
A	O
special	O
case	O
of	O
a	O
chemical	O
synapse	B-Application
is	O
the	O
neuromuscular	O
junction	O
,	O
in	O
which	O
the	O
axon	B-Algorithm
of	O
a	O
motor	O
neuron	O
terminates	O
on	O
a	O
muscle	O
fiber	O
.	O
</s>
<s>
However	O
,	O
the	O
acetylcholine	O
does	O
not	O
remain	O
bound	O
;	O
rather	O
,	O
it	O
dissociates	O
and	O
is	O
hydrolyzed	O
by	O
the	O
enzyme	O
,	O
acetylcholinesterase	O
,	O
located	O
in	O
the	O
synapse	B-Application
.	O
</s>
<s>
Some	O
poisons	O
inactivate	O
acetylcholinesterase	O
to	O
prevent	O
this	O
control	O
,	O
such	O
as	O
the	O
nerve	O
agents	O
sarin	O
and	O
tabun	O
,	O
and	O
the	O
insecticides	B-Application
diazinon	O
and	O
malathion	O
.	O
</s>
<s>
The	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
differs	O
from	O
the	O
neuronal	O
action	B-Algorithm
potential	I-Algorithm
by	O
having	O
an	O
extended	O
plateau	O
,	O
in	O
which	O
the	O
membrane	O
is	O
held	O
at	O
a	O
high	O
voltage	O
for	O
a	O
few	O
hundred	O
milliseconds	O
prior	O
to	O
being	O
repolarized	O
by	O
the	O
potassium	O
current	O
as	O
usual	O
.	O
</s>
<s>
The	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
plays	O
an	O
important	O
role	O
in	O
coordinating	O
the	O
contraction	O
of	O
the	O
heart	O
.	O
</s>
<s>
The	O
cardiac	O
cells	O
of	O
the	O
sinoatrial	O
node	O
provide	O
the	O
pacemaker	B-Algorithm
potential	I-Algorithm
that	O
synchronizes	O
the	O
heart	O
.	O
</s>
<s>
The	O
action	B-Algorithm
potentials	I-Algorithm
of	O
those	O
cells	O
propagate	O
to	O
and	O
through	O
the	O
atrioventricular	O
node	O
(	O
AV	O
node	O
)	O
,	O
which	O
is	O
normally	O
the	O
only	O
conduction	O
pathway	O
between	O
the	O
atria	O
and	O
the	O
ventricles	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
from	O
the	O
AV	O
node	O
travel	O
through	O
the	O
bundle	B-Algorithm
of	I-Algorithm
His	I-Algorithm
and	O
thence	O
to	O
the	O
Purkinje	B-Algorithm
fibers	I-Algorithm
.	O
</s>
<s>
Conversely	O
,	O
anomalies	O
in	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
—	O
whether	O
due	O
to	O
a	O
congenital	O
mutation	O
or	O
injury	O
—	O
can	O
lead	O
to	O
human	O
pathologies	O
,	O
especially	O
arrhythmias	B-Application
.	O
</s>
<s>
Several	O
anti-arrhythmia	O
drugs	O
act	O
on	O
the	O
cardiac	B-Algorithm
action	I-Algorithm
potential	I-Algorithm
,	O
such	O
as	O
quinidine	O
,	O
lidocaine	O
,	O
beta	O
blockers	O
,	O
and	O
verapamil	O
.	O
</s>
<s>
The	O
action	B-Algorithm
potential	I-Algorithm
in	O
a	O
normal	O
skeletal	O
muscle	O
cell	O
is	O
similar	O
to	O
the	O
action	B-Algorithm
potential	I-Algorithm
in	O
neurons	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
result	O
from	O
the	O
depolarization	O
of	O
the	O
cell	O
membrane	O
(	O
the	O
sarcolemma	O
)	O
,	O
which	O
opens	O
voltage-sensitive	O
sodium	O
channels	O
;	O
these	O
become	O
inactivated	O
and	O
the	O
membrane	O
is	O
repolarized	O
through	O
the	O
outward	O
current	O
of	O
potassium	O
ions	O
.	O
</s>
<s>
The	O
resting	O
potential	O
prior	O
to	O
the	O
action	B-Algorithm
potential	I-Algorithm
is	O
typically	O
−90mV	O
,	O
somewhat	O
more	O
negative	O
than	O
typical	O
neurons	O
.	O
</s>
<s>
The	O
muscle	O
action	B-Algorithm
potential	I-Algorithm
lasts	O
roughly	O
2	O
–	O
4ms	O
,	O
the	O
absolute	O
refractory	O
period	O
is	O
roughly	O
1	O
–	O
3ms	O
,	O
and	O
the	O
conduction	O
velocity	O
along	O
the	O
muscle	O
is	O
roughly	O
5m/s	O
.	O
</s>
<s>
The	O
action	B-Algorithm
potential	I-Algorithm
releases	O
calcium	O
ions	O
that	O
free	O
up	O
the	O
tropomyosin	O
and	O
allow	O
the	O
muscle	O
to	O
contract	O
.	O
</s>
<s>
Muscle	O
action	B-Algorithm
potentials	I-Algorithm
are	O
provoked	O
by	O
the	O
arrival	O
of	O
a	O
pre-synaptic	O
neuronal	O
action	B-Algorithm
potential	I-Algorithm
at	O
the	O
neuromuscular	O
junction	O
,	O
which	O
is	O
a	O
common	O
target	O
for	O
neurotoxins	O
.	O
</s>
<s>
The	O
fundamental	O
difference	O
from	O
animal	O
action	B-Algorithm
potentials	I-Algorithm
is	O
that	O
the	O
depolarization	O
in	O
plant	O
cells	O
is	O
not	O
accomplished	O
by	O
an	O
uptake	O
of	O
positive	O
sodium	O
ions	O
,	O
but	O
by	O
release	O
of	O
negative	O
chloride	O
ions	O
.	O
</s>
<s>
In	O
1906	O
,	O
J	O
.	O
C	O
.	O
Bose	O
published	O
the	O
first	O
measurements	O
of	O
action	B-Algorithm
potentials	I-Algorithm
in	O
plants	O
,	O
which	O
had	O
previously	O
been	O
discovered	O
by	O
Burdon-Sanderson	O
and	O
Darwin	O
.	O
</s>
<s>
However	O
,	O
plenty	O
of	O
research	O
has	O
been	O
done	O
on	O
action	B-Algorithm
potentials	I-Algorithm
and	O
how	O
they	O
affect	O
movement	O
and	O
clockwork	O
within	O
the	O
Venus	O
flytrap	O
.	O
</s>
<s>
The	O
lower	O
resting	O
potential	O
makes	O
it	O
easier	O
to	O
activate	O
an	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
This	O
receptor	O
then	O
activates	O
an	O
action	B-Algorithm
potential	I-Algorithm
which	O
lasts	O
around	O
1.5	O
ms.	O
</s>
<s>
When	O
the	O
second	O
action	B-Algorithm
potential	I-Algorithm
is	O
fired	O
within	O
the	O
time	O
interval	O
,	O
it	O
reaches	O
the	O
Calcium	O
threshold	O
to	O
depolarize	O
the	O
cell	O
,	O
closing	O
the	O
trap	O
on	O
the	O
prey	O
within	O
a	O
fraction	O
of	O
a	O
second	O
.	O
</s>
<s>
Together	O
with	O
the	O
subsequent	O
release	O
of	O
positive	O
potassium	O
ions	O
the	O
action	B-Algorithm
potential	I-Algorithm
in	O
plants	O
involves	O
an	O
osmotic	O
loss	O
of	O
salt	O
(	O
KCl	O
)	O
.	O
</s>
<s>
Whereas	O
,	O
the	O
animal	O
action	B-Algorithm
potential	I-Algorithm
is	O
osmotically	O
neutral	O
because	O
equal	O
amounts	O
of	O
entering	O
sodium	O
and	O
leaving	O
potassium	O
cancel	O
each	O
other	O
osmotically	O
.	O
</s>
<s>
It	O
is	O
likely	O
that	O
the	O
familiar	O
signaling	O
function	O
of	O
action	B-Algorithm
potentials	I-Algorithm
in	O
some	O
vascular	O
plants	O
(	O
e.g.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
are	O
found	O
throughout	O
multicellular	O
organisms	O
,	O
including	O
plants	O
,	O
invertebrates	O
such	O
as	O
insects	O
,	O
and	O
vertebrates	O
such	O
as	O
reptiles	B-Language
and	O
mammals	O
.	O
</s>
<s>
Sponges	O
seem	O
to	O
be	O
the	O
main	O
phylum	O
of	O
multicellular	O
eukaryotes	O
that	O
does	O
not	O
transmit	O
action	B-Algorithm
potentials	I-Algorithm
,	O
although	O
some	O
studies	O
have	O
suggested	O
that	O
these	O
organisms	O
have	O
a	O
form	O
of	O
electrical	O
signaling	O
,	O
too	O
.	O
</s>
<s>
The	O
resting	O
potential	O
,	O
as	O
well	O
as	O
the	O
size	O
and	O
duration	O
of	O
the	O
action	B-Algorithm
potential	I-Algorithm
,	O
have	O
not	O
varied	O
much	O
with	O
evolution	O
,	O
although	O
the	O
conduction	O
velocity	O
does	O
vary	O
dramatically	O
with	O
axonal	O
diameter	O
and	O
myelination	O
.	O
</s>
<s>
Given	O
its	O
conservation	O
throughout	O
evolution	O
,	O
the	O
action	B-Algorithm
potential	I-Algorithm
seems	O
to	O
confer	O
evolutionary	O
advantages	O
.	O
</s>
<s>
One	O
function	O
of	O
action	B-Algorithm
potentials	I-Algorithm
is	O
rapid	O
,	O
long-range	O
signaling	O
within	O
the	O
organism	O
;	O
the	O
conduction	O
velocity	O
can	O
exceed	O
110m/s	O
,	O
which	O
is	O
one-third	O
the	O
speed	O
of	O
sound	O
.	O
</s>
<s>
Being	O
an	O
all-or-none	O
signal	O
that	O
does	O
not	O
decay	O
with	O
transmission	O
distance	O
,	O
the	O
action	B-Algorithm
potential	I-Algorithm
has	O
similar	O
advantages	O
to	O
digital	O
electronics	O
.	O
</s>
<s>
The	O
integration	O
of	O
various	O
dendritic	O
signals	O
at	O
the	O
axon	B-Algorithm
hillock	O
and	O
its	O
thresholding	O
to	O
form	O
a	O
complex	O
train	O
of	O
action	B-Algorithm
potentials	I-Algorithm
is	O
another	O
form	O
of	O
computation	O
,	O
one	O
that	O
has	O
been	O
exploited	O
biologically	O
to	O
form	O
central	O
pattern	O
generators	O
and	O
mimicked	O
in	O
artificial	B-Architecture
neural	I-Architecture
networks	I-Architecture
.	O
</s>
<s>
Even	O
modern	O
single-celled	O
bacteria	O
can	O
utilize	O
action	B-Algorithm
potentials	I-Algorithm
to	O
communicate	O
with	O
other	O
bacteria	O
in	O
the	O
same	O
biofilm	O
.	O
</s>
<s>
The	O
study	O
of	O
action	B-Algorithm
potentials	I-Algorithm
has	O
required	O
the	O
development	O
of	O
new	O
experimental	O
methods	O
.	O
</s>
<s>
The	O
initial	O
work	O
,	O
prior	O
to	O
1955	O
,	O
was	O
carried	O
out	O
primarily	O
by	O
Alan	O
Lloyd	O
Hodgkin	O
and	O
Andrew	O
Fielding	O
Huxley	O
,	O
who	O
were	O
,	O
along	O
John	O
Carew	O
Eccles	O
,	O
awarded	O
the	O
1963	O
Nobel	O
Prize	O
in	O
Physiology	O
or	O
Medicine	O
for	O
their	O
contribution	O
to	O
the	O
description	O
of	O
the	O
ionic	O
basis	O
of	O
nerve	B-Algorithm
conduction	I-Algorithm
.	O
</s>
<s>
It	O
focused	O
on	O
three	O
goals	O
:	O
isolating	O
signals	O
from	O
single	O
neurons	O
or	O
axons	B-Algorithm
,	O
developing	O
fast	O
,	O
sensitive	O
electronics	O
,	O
and	O
shrinking	O
electrodes	O
enough	O
that	O
the	O
voltage	O
inside	O
a	O
single	O
cell	O
could	O
be	O
recorded	O
.	O
</s>
<s>
The	O
first	O
problem	O
was	O
solved	O
by	O
studying	O
the	O
giant	O
axons	B-Algorithm
found	O
in	O
the	O
neurons	O
of	O
the	O
squid	B-Protocol
(	O
Loligo	O
forbesii	O
and	O
Doryteuthis	O
pealeii	O
,	O
at	O
the	O
time	O
classified	O
as	O
Loligo	O
pealeii	O
)	O
.	O
</s>
<s>
These	O
axons	B-Algorithm
are	O
so	O
large	O
in	O
diameter	O
(	O
roughly	O
1mm	O
,	O
or	O
100-fold	O
larger	O
than	O
a	O
typical	O
neuron	O
)	O
that	O
they	O
can	O
be	O
seen	O
with	O
the	O
naked	O
eye	O
,	O
making	O
them	O
easy	O
to	O
extract	O
and	O
manipulate	O
.	O
</s>
<s>
However	O
,	O
they	O
are	O
not	O
representative	O
of	O
all	O
excitable	O
cells	O
,	O
and	O
numerous	O
other	O
systems	O
with	O
action	B-Algorithm
potentials	I-Algorithm
have	O
been	O
studied	O
.	O
</s>
<s>
The	O
second	O
problem	O
was	O
addressed	O
with	O
the	O
crucial	O
development	O
of	O
the	O
voltage	O
clamp	O
,	O
which	O
permitted	O
experimenters	O
to	O
study	O
the	O
ionic	O
currents	O
underlying	O
an	O
action	B-Algorithm
potential	I-Algorithm
in	O
isolation	O
,	O
and	O
eliminated	O
a	O
key	O
source	O
of	O
electronic	O
noise	O
,	O
the	O
current	O
IC	O
associated	O
with	O
the	O
capacitance	O
C	O
of	O
the	O
membrane	O
.	O
</s>
<s>
The	O
third	O
problem	O
,	O
that	O
of	O
obtaining	O
electrodes	O
small	O
enough	O
to	O
record	O
voltages	O
within	O
a	O
single	O
axon	B-Algorithm
without	O
perturbing	O
it	O
,	O
was	O
solved	O
in	O
1949	O
with	O
the	O
invention	O
of	O
the	O
glass	O
micropipette	O
electrode	O
,	O
which	O
was	O
quickly	O
adopted	O
by	O
other	O
researchers	O
.	O
</s>
<s>
Action	B-Algorithm
potentials	I-Algorithm
may	O
also	O
be	O
recorded	O
with	O
small	O
metal	O
electrodes	O
placed	O
just	O
next	O
to	O
a	O
neuron	O
,	O
with	O
neurochips	O
containing	O
EOSFETs	B-Algorithm
,	O
or	O
optically	O
with	O
dyes	O
that	O
are	O
sensitive	O
to	O
Ca2+	O
or	O
to	O
voltage	O
.	O
</s>
<s>
Optical	B-Algorithm
imaging	I-Algorithm
technologies	O
have	O
been	O
developed	O
in	O
recent	O
years	O
to	O
measure	O
action	B-Algorithm
potentials	I-Algorithm
,	O
either	O
via	O
simultaneous	O
multisite	O
recordings	O
or	O
with	O
ultra-spatial	O
resolution	O
.	O
</s>
<s>
Using	O
voltage-sensitive	O
dyes	O
,	O
action	B-Algorithm
potentials	I-Algorithm
have	O
been	O
optically	O
recorded	O
from	O
a	O
tiny	O
patch	O
of	O
cardiomyocyte	O
membrane	O
.	O
</s>
<s>
Several	O
neurotoxins	O
,	O
both	O
natural	O
and	O
synthetic	O
,	O
are	O
designed	O
to	O
block	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
Tetrodotoxin	O
from	O
the	O
pufferfish	O
and	O
saxitoxin	O
from	O
the	O
Gonyaulax	O
(	O
the	O
dinoflagellate	O
genus	O
responsible	O
for	O
"	O
red	O
tides	O
"	O
)	O
block	O
action	B-Algorithm
potentials	I-Algorithm
by	O
inhibiting	O
the	O
voltage-sensitive	O
sodium	O
channel	O
;	O
similarly	O
,	O
dendrotoxin	O
from	O
the	O
black	O
mamba	O
snake	O
inhibits	O
the	O
voltage-sensitive	O
potassium	O
channel	O
.	O
</s>
<s>
Neurotoxins	O
aimed	O
at	O
the	O
ion	O
channels	O
of	O
insects	O
have	O
been	O
effective	O
insecticides	B-Application
;	O
one	O
example	O
is	O
the	O
synthetic	O
permethrin	O
,	O
which	O
prolongs	O
the	O
activation	O
of	O
the	O
sodium	O
channels	O
involved	O
in	O
action	B-Algorithm
potentials	I-Algorithm
.	O
</s>
<s>
The	O
role	O
of	O
electricity	O
in	O
the	O
nervous	O
systems	O
of	O
animals	O
was	O
first	O
observed	O
in	O
dissected	O
frogs	B-Algorithm
by	O
Luigi	O
Galvani	O
,	O
who	O
studied	O
it	O
from	O
1791	O
to	O
1797	O
.	O
</s>
<s>
Galvani	O
's	O
results	O
stimulated	O
Alessandro	O
Volta	O
to	O
develop	O
the	O
Voltaic	B-Architecture
pile	I-Architecture
—	O
the	O
earliest-known	O
electric	O
battery	O
—	O
with	O
which	O
he	O
studied	O
animal	O
electricity	O
(	O
such	O
as	O
electric	O
eels	O
)	O
and	O
the	O
physiological	O
responses	O
to	O
applied	O
direct-current	O
voltages	O
.	O
</s>
<s>
Matteucci	O
's	O
work	O
inspired	O
the	O
German	O
physiologist	O
,	O
Emil	O
du	O
Bois-Reymond	O
,	O
who	O
discovered	O
the	O
action	B-Algorithm
potential	I-Algorithm
in	O
1843	O
.	O
</s>
<s>
The	O
conduction	O
velocity	O
of	O
action	B-Algorithm
potentials	I-Algorithm
was	O
first	O
measured	O
in	O
1850	O
by	O
du	O
Bois-Reymond	O
'	O
s	O
friend	O
,	O
Hermann	O
von	O
Helmholtz	O
.	O
</s>
<s>
In	O
1902	O
and	O
again	O
in	O
1912	O
,	O
Julius	O
Bernstein	O
advanced	O
the	O
hypothesis	O
that	O
the	O
action	B-Algorithm
potential	I-Algorithm
resulted	O
from	O
a	O
change	O
in	O
the	O
permeability	O
of	O
the	O
axonal	O
membrane	O
to	O
ions	O
.	O
</s>
<s>
Bernstein	O
's	O
hypothesis	O
was	O
confirmed	O
by	O
Ken	O
Cole	O
and	O
Howard	O
Curtis	O
,	O
who	O
showed	O
that	O
membrane	O
conductance	O
increases	O
during	O
an	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
In	O
1907	O
,	O
Louis	O
Lapicque	O
suggested	O
that	O
the	O
action	B-Algorithm
potential	I-Algorithm
was	O
generated	O
as	O
a	O
threshold	O
was	O
crossed	O
,	O
what	O
would	O
be	O
later	O
shown	O
as	O
a	O
product	O
of	O
the	O
dynamical	O
systems	O
of	O
ionic	O
conductances	O
.	O
</s>
<s>
In	O
1949	O
,	O
Alan	O
Hodgkin	O
and	O
Bernard	O
Katz	O
refined	O
Bernstein	O
's	O
hypothesis	O
by	O
considering	O
that	O
the	O
axonal	O
membrane	O
might	O
have	O
different	O
permeabilities	O
to	O
different	O
ions	O
;	O
in	O
particular	O
,	O
they	O
demonstrated	O
the	O
crucial	O
role	O
of	O
the	O
sodium	O
permeability	O
for	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
They	O
made	O
the	O
first	O
actual	O
recording	O
of	O
the	O
electrical	O
changes	O
across	O
the	O
neuronal	O
membrane	O
that	O
mediate	O
the	O
action	B-Algorithm
potential	I-Algorithm
.	O
</s>
<s>
This	O
line	O
of	O
research	O
culminated	O
in	O
the	O
five	O
1952	O
papers	O
of	O
Hodgkin	O
,	O
Katz	O
and	O
Andrew	O
Huxley	O
,	O
in	O
which	O
they	O
applied	O
the	O
voltage	O
clamp	O
technique	O
to	O
determine	O
the	O
dependence	O
of	O
the	O
axonal	O
membrane	O
's	O
permeabilities	O
to	O
sodium	O
and	O
potassium	O
ions	O
on	O
voltage	O
and	O
time	O
,	O
from	O
which	O
they	O
were	O
able	O
to	O
reconstruct	O
the	O
action	B-Algorithm
potential	I-Algorithm
quantitatively	O
.	O
</s>
<s>
Mathematical	O
and	O
computational	B-Application
models	I-Application
are	O
essential	O
for	O
understanding	O
the	O
action	B-Algorithm
potential	I-Algorithm
,	O
and	O
offer	O
predictions	O
that	O
may	O
be	O
tested	O
against	O
experimental	O
data	O
,	O
providing	O
a	O
stringent	O
test	O
of	O
a	O
theory	O
.	O
</s>
<s>
The	O
most	O
important	O
and	O
accurate	O
of	O
the	O
early	O
neural	O
models	O
is	O
the	O
Hodgkin	O
–	O
Huxley	O
model	O
,	O
which	O
describes	O
the	O
action	B-Algorithm
potential	I-Algorithm
by	O
a	O
coupled	O
set	O
of	O
four	O
ordinary	O
differential	O
equations	O
(	O
ODEs	O
)	O
.	O
</s>
<s>
However	O
the	O
simple	O
models	O
of	O
generator	O
potential	O
and	O
action	B-Algorithm
potential	I-Algorithm
fail	O
to	O
accurately	O
reproduce	O
the	O
near	O
threshold	O
neural	O
spike	B-Algorithm
rate	O
and	O
spike	B-Algorithm
shape	O
,	O
specifically	O
for	O
the	O
mechanoreceptors	O
like	O
the	O
Pacinian	B-Algorithm
corpuscle	I-Algorithm
.	O
</s>
<s>
More	O
modern	O
research	O
has	O
focused	O
on	O
larger	O
and	O
more	O
integrated	O
systems	O
;	O
by	O
joining	O
action-potential	O
models	O
with	O
models	O
of	O
other	O
parts	O
of	O
the	O
nervous	O
system	O
(	O
such	O
as	O
dendrites	O
and	O
synapses	B-Application
)	O
,	O
researchers	O
can	O
study	O
neural	O
computation	O
and	O
simple	O
reflexes	B-Algorithm
,	O
such	O
as	O
escape	O
reflexes	B-Algorithm
and	O
others	O
controlled	O
by	O
central	O
pattern	O
generators	O
.	O
</s>
