Download Mucus: the sticky stuff Do electrical currents drive mucus production

The electricity of mucus
Greer Arthur1*, Erol Gaillard1, Peter Bradding1
Department of Infection, Immunity and Inflammation1. Glenfield Hospital, Leicester. [email protected]*
Mucus: the sticky stuff
If the ion channel responsible for driving mucus
production can be identified, then blocking this
channel could reduce the size of this electrical signal
and consequently prevent excessive mucus
production
This project focuses on the ion channel, KCa3.1, and
whether it plays a role in mucus production.
Results
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Mucus-producing cells express KCa3.1
KCa3.1
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MUC5AC
This graph of quantified
immunohistochemistry
data shows that the airway
epithelium of patients with
asthma display significantly
larger quantities of KCa3.1
than the airway epithelium
of healthy control subjects.
These electrical signals are controlled by ion channels
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The size of the electrical signal conducted by KCa3.1
was compared in healthy cells and in asthmatic cells
to investigate whether there were any differences
between health and disease
o
n
a
o
m
th
s
A
lt
a
e
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To investigate the potential of KCa3.1 as a target
for asthma treatment
Immunohistochemistry (a method of identifying your
protein of interest, such as your ion channel or
mucus, using an antibody-based reaction with a
coloured-end product) was used to investigate
whether mucus-producing cells express the ion
channel of interest, KCa3.1
tr
ti
To examine the role of KCa3.1 in mucus
production
Methodology
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Research aims

Patients with asthma have higher levels of KCa3.1
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expression
ls
Normal human airway cells have a set of mechanisms to
regulate this mucus production, and some of these mechanisms
are thought to be operated by electrical signals passing across
the cell membrane
c
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Asthma is a respiratory disease that is susceptible to airway
blockage by mucus, and this can be fatal.
y

If an ion channel responsible for controlling mucus
production becomes overactive, this could result in
the creation of an abnormally large electrical
signal, and result in too much mucus being
produced
These images show that mucus-producing cells of the airways,
identified by their MUC5AC expression, also express the ion channel
of interest, KCa3.1. This indicates that this ion channel might play a
role in the functioning of mucus-producing cells. Cells expressing
KCa3.1 and MUC5AC are stained red and circled in yellow.
H
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h
Mucus production is tightly regulated to ensure that the
quantity of mucus within the airways is beneficial and healthy. If
this process becomes faulty, it can lead to blockage of the
airways.
There are a large number of different types of ion
channels but each controls its own specific electrical
signal, which in turn controls a specific mechanism,
such as mucus production
s
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A r e a f r a c t io n ( % )
Mucus is a complex gel that forms a protective barrier within the
airways, allowing the trapping of bacteria and harmful particles.
K C a3 .1
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Do electrical currents drive mucus production?
Asthmatic cells display larger KCa3.1 currents than
healthy cells
This graph of patch clamp
electrophysiology data
shows that the size of the
electrical current controlled
by KCa3.1 activity was
significantly larger in
asthmatic cells in
comparison to healthy
control cells
Im ( p A )
500
IK C a 3 . 1 A s th m a tic
IK C a 3 . 1 H e a lth y
0
-1 0 0
-5 0
0
50
100
Vm
em
(m V )
Conclusions

These results demonstrate that mucus-producing cells express KCa3.1, indicating that KCa3.1 plays a role in the functioning and
activity of mucus-producing cells – the next step is to discover what this role is

Findings also show that KCa3.1 expression and the size of the channel’s electrical signal is larger in asthmatic airway cells in
comparison to healthy cells, suggesting that abnormal KCa3.1 expression and activity is a feature of asthma