Ion Channels in Cell Communication
Gated Channels & Cell
Communication
Ion channels
•
Ion channels
are pore-forming membrane
proteins that allow ions to pass through the channel
pore.
•
Their functions include gating the flow of ions across
the cell membrane, controlling the flow of ions
across secretory and epithelial cells, and
regulating cell volume.
•
Ion channels are present in the membranes of all cells.
•
Ion channels are one of the two classes
of ionophoric proteins, along with ion transporters.
•
The study of ion channels often
involves biophysics, electrophysiology,
and pharmacology, while using techniques
including voltage clamp, patch
clamp, immunohistochemistry, X-ray
crystallography, fluoroscopy, and RT-PCR.
•
Their classification as molecules is referred to
as channelomics.
•
There are two distinctive features of ion channels that
differentiate them from other types of ion transporter
proteins:
•
The rate of ion transport through the channel is very high
(often 10
6
ions per second or greater).
•
Ions pass through channels down their electrochemical
gradient, which is a function of ion concentration and
membrane potential, "downhill", without the input (or
help) of metabolic energy
B
i
o
l
og
ic
a
l
R
o
l
e
s
•
Conductance
of
Nerve
impulse,
generation
of
action
potential,
synaptic
transmission.
•
Cardiac,
skeletal
and
smooth
muscle
contraction.
•
Epithelial
transport
of
nutrients
and
ions.
•
T-cell
activation
(immune
regulation).
•
Pancreatic
beta
cell
insulin
release.
Gating Channels
•
Ion channels may be classified by gating, i.e. what opens and closes the
channels.
•
2 Types:
•
Voltage Gated
•
Ligand Gated
•
Voltage-gated ion channels open or close depending on the voltage
gradient across the plasma membrane.
•
While ligand-gated ion channels open or close depending on binding
of ligands to the channel.
Voltage Gated
•
Voltage
sensitive
•
Conformational
change
in
response
to
the
potential
gradient.
•
Generally
ion
specific.
•
Important
for
excitable
cells
like
neurons.
•
Distributed
along
the
axon
and
soma
of
the
neurons.
T
yp
e
s of
V
o
l
ta
g
e
G
a
t
e
d
C
h
a
nn
el
s
V
o
l
t
a
g
e
G
a
t
e
d
S
o
d
i
u
m
C
h
a
n
n
e
l
s
•
9
m
e
m
be
r
s
,
r
e
s
pons
ibl
e
f
o
r membrane
depolarization
in
action
potential
generation.
Voltage
Gated
Calcium
Channels
•
10
members, play
an
important
role
in
both
linking
muscle
excitation
with
contraction
as
well
as
neuronal
excitation
with
transmitter
release.
Voltage
Gated
Potassium
Channels
•
40members,
role
in repolarization of
cell
membrane
after
action potential
Transient
receptor
potential
channels
(TRP
channels):
•
28
types,
some
of
them
are
voltage
gated,
named
after
their
role
.
Present in
Drosophila
phototransduction.
Hyperpolarization-activated
cyclic
nucleotide-gated
channel
•
pacemaking
channels
in
the
heart,
sensitive
to
cAMP,
cGMP
that
alter
the
voltage
sensitivity
of
the
channels.
Voltage
sensitive
proton
channels
•
helps
in
acid
extrusion
from
cell,
ph
a
goc
y
t
os
i
s
,
s
t
r
ong
l
y
p
H
r
e
g
u
l
a
t
e
d.
Structure
•
Several
subunits
with
a
central
pore.
•
Ion
specific,
but
ions
with
similar
charge
and
size
can
enter.
•
Functionality
governed
by
3
main
parts-
the
voltage
sensor,
the
pore
and
the
gate.
•
Na,
K
and
Ca
channels
have
4
transmembrane
alpha
subunits
surrounding
the
pore.
•
Six
subunits:
S1-S6.
•
S1-S4:
Voltage
sensing
region,
S5-S6:
Gate
and
pore.
•
Regulatory
beta
subunits.
Mechanism of Action
Mechanism
•
F
o
r
p
o
t
as
siu
m
c
h
a
n
n
e
l
:
•
When a
po
t
en
ti
a
l
d
i
f
f
e
r
e
n
c
e
i
s
i
n
t
r
odu
c
e
d
ov
e
r
t
h
e
m
e
m
b
r
a
n
e
,
t
h
e
a
ssoc
i
a
t
e
d
e
l
ec
t
r
i
c
fi
e
ld
induces
a
conformational
change
in
the
potassium
channel.
•
The
conformational
change
distorts
the
shape
of
the
channel
proteins
sufficiently
such
that
the
cavity,
or
channel,
opens
to
allow
influx
or
efflux
to
occur
across
the
membrane.
Voltage
sensing
in
Na
and
Ca
channels:
•
Positive
charges
in
the
voltage
sensing
domain,
p
resence
of
Arginine
and
histidine
repeats
in
this
segment.
•
Gate
acts
as
a
mechanical
obstruction
to
ion
flow.
•
Channel
closes
milliseconds
after
opening.
Ligand Gated Channels
•
G
r
ou
p
o
f
t
r
ans
m
e
m
b
r
a
ne i
o
n
chan
n
e
ls
that
allow the
passing
of
several ions upon the binding of specific chemical
m
e
sseng
e
r
l
i
k
e
n
e
u
r
o
t
r
ans
m
itt
e
r
s
.
•
Two Domains – transmembrane domains
including
channel
pore,
Extracellular
domain
including
ligand
binding
site.
•
Function:
Conversion
of
presynaptic
chemical
signal
quickly
and
effectively
into
post-synaptic
electrical
signal.
•
Three
super
families:
cys-loop receptors ,
I
ono
t
rop
i
c
Gl
u
ta
m
ate
Rec
e
p
t
or, ATP Gated Channels
Cys-loop receptors
•
Characteristic
loop
formed
by
a
disulfide
bond
between
two
cysteine
residues
in
t
h
e
N
t
e
r
m
i
na
l
e
x
t
r
ace
llul
a
r
do
m
a
i
n
.
•
P
r
o
vid
e
s
spec
if
i
c
i
t
y
f
o
r
•
Acetyl Choline, Seratonin, Glycine, Glutatamate,
γ-
a
m
in
obu
t
yric acid
•
Structural elements are well conserved with a
e
x
t
r
a
c
e
ll
u
l
a
r
d
o
m
a
i
n
(E
C
D
)
harbouring
an
alpha-helix
and 10 beta strands
•
Following
the ECD four transmembrane segments (TMSs) are present.
I
ono
t
rop
i
c
Gl
u
ta
m
ate
Rec
e
p
t
or
•
Binds
to
Glutamate.
•
Consists
of
a
tetramer.
•
E
a
c
h
s
ub
-
u
nit
consists
of extracellular amino
terminal domain (ATD) which is
i
n
v
o
l
v
e
d
in
t
e
t
r
a
m
e
r
ass
e
m
b
l
y,
a
n
e
x
t
ra
ce
ll
u
l
a
r
l
i
gan
d
b
i
nd
i
n
g
d
o
m
a
i
n
L
B
D
,
w
h
ic
h
bi
nd
s
g
lut
a
m
a
te,
an
d
a
transmembrane
domain
TMD,
which
forms
the
ion
channel.
•
Each
subunit
of
the
tetramer
has
a
binding
site
for
glutamate
formed
by
the
two
LBD.
A
T
P
Ga
t
e
d
c
h
a
nn
el
s
•
Bind
to
ATP
in
order
to
open.
•
They
form
trimers
with
two
transmembrane
helices
per
subunit
and
both
the
C
and
N
termini
on
the
intracellular
side.
M
e
c
h
an
i
s
m
a
nd
R
e
c
e
p
t
o
r
s
Cell communication
•
Cell signaling
is part of any communication process that governs basic
activities of cells and coordinates all cell actions.
•
The ability of cells to perceive and correctly respond to their
microenvironment is the basis of development, tissue repair,
and immunity, as well as normal tissue homeostasis.
•
Errors in signaling interactions and cellular information processing are
responsible for diseases such as cancer, autoimmunity, and diabetes.
•
By understanding cell signaling, diseases may be treated more effectively
and, theoretically, artificial tissues may be created.
Form of Signaling
•
Cells communicate via various types of signaling that allow chemicals to travel to
target sites in order to elicit a response.
•
Paracrine signaling occurs between local cells where the signals elicit quick
responses and last only a short amount of time due to the degradation of the
paracrine ligands.
•
Endocrine signaling occurs between distant cells and is mediated by hormones
released from specific endocrine cells that travel to target cells, producing a
slower, long-lasting response.
•
Autocrine signals are produced by signaling cells that can also bind to the ligand
that is released, which means the signaling cell and the target cell can be the same
or a similar cell.
•
Direct signaling can occur by transferring signaling molecules across gap
junctions between neighboring cells.
Types of Molecules
•
Intracellular receptors are located in the cytoplasm of the cell and are
activated by hydrophobic ligand molecules that can pass through the
plasma membrane.
•
Cell-surface receptors bind to an external ligand molecule and convert an
extracellular signal into an intracellular signal.
•
Three general categories of cell-surface receptors include: ion -channel,
G- protein, and enzyme -linked protein receptors.
•
Ion channel -linked receptors bind a ligand and open a channel through
the membrane that allows specific ions to pass through.
•
G-protein-linked receptors bind a ligand and activate a membrane protein
called a G-protein, which then interacts with either an ion channel or an
enzyme in the membrane.
•
Enzyme-linked receptors are cell-surface receptors with intracellular
domains that are associated with an enzyme.
Signaling Molecules
•
Produced by signaling cells and the subsequent
binding to receptors in target cells, ligands act as
chemical signals that travel to the target cells to
coordinate responses.
•
The types of molecules that serve as ligands are
incredibly varied and range from small proteins
to small ions like calcium (Ca
2+
).
•
Small Hydrophobic ligands
•
Water Soluble ligands
•
Other Ligands
Small Hydrophobic ligands
•
Small hydrophobic ligands can directly diffuse through the plasma membrane and
interact with internal receptors.
•
Important members of this class of ligands are the steroid hormones.
•
Steroids are lipids that have a hydrocarbon skeleton with four fused rings;
different steroids have different functional groups attached to the carbon skeleton.
•
Steroid hormones include the female sex hormone, estradiol, which is a type of
estrogen; the male sex hormone, testosterone; and cholesterol, which is an
important structural component of biological membranes and a precursor of
steriod hormones.
•
Other hydrophobic hormones include thyroid hormones and vitamin D.
•
In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins
while they are being transported through the bloodstream.
Water-soluble ligands
•
Water-soluble ligands are polar and, therefore, cannot pass through
the plasma membrane unaided; sometimes, they are too large to
pass through the membrane at all.
•
Most water-soluble ligands bind to the extracellular domain of cell
surface receptors.
•
The binding of these ligands to these receptors results in a series
of cellular changes.
•
These water soluble ligands are quite diverse and include small
molecules, peptides, and proteins.
Other Ligands
•
Nitric oxide (NO) is a gas that also acts as a ligand.
•
It is able to diffuse directly across the plasma membrane; one of its
roles is to interact with receptors in smooth muscle and induce
relaxation of the tissue.
•
NO has a very short half-life; therefore, it only functions over short
distances.
•
Nitroglycerin, a treatment for heart disease, acts by triggering the
release of NO, which causes blood vessels to dilate (expand), thus
restoring blood flow to the heart.
Ion channels play a crucial role in cell communication by allowing ions to pass through cell membranes, controlling various cellular functions. Their high transport rate and electrochemical gradient differentiate them from other ion transporter proteins. Ion channels have diverse biological roles, influencing nerve impulse conductance, muscle contraction, nutrient transport, immune regulation, and more. They are classified based on gating mechanisms like voltage-gated and ligand-gated channels for regulating ion flow. Voltage-gated channels are crucial for excitable cells like neurons.
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Presentation Transcript
Gated Channels & Cell Communication
Ion channels Ion proteins that allow ions to pass through the channel pore. Their functions include gating the flow of ions across the cell membrane, controlling the flow of across secretory and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of ionophoric proteins, along with ion transporters. channels are pore-forming membrane ions and epithelial cells, of the two classes
The involves and pharmacology, while using techniques including voltage clamp, immunohistochemistry, crystallography, fluoroscopy, and RT-PCR. Their classification as molecules is referred to as channelomics. study of ion channels electrophysiology, often biophysics, clamp, patch X-ray
There are two distinctive features of ion channels that differentiate them from other types of ion transporter proteins: The rate of ion transport through the channel is very high (often 106ions per second or greater). Ions pass through channels down their electrochemical gradient, which is a function of ion concentration and membrane potential, "downhill", without the input (or help) of metabolic energy
Biological Roles Conductance of Nerve impulse, generation of action potential, synaptic transmission. Cardiac, skeletal and smooth muscle contraction. Epithelial transport of nutrients and ions. T-cell activation (immune regulation). Pancreatic beta cell insulin release.
Gating Channels Ion channels may be classified by gating, i.e. what opens and closes the channels. 2 Types: Voltage Gated Ligand Gated Voltage-gated ion channels open or close depending on the voltage gradient across the plasma membrane. While ligand-gated ion channels open or close depending on binding of ligands to the channel.
Voltage Gated Voltage sensitive Conformational change in response to the potential gradient. Generally ion specific. Important for excitable cells like neurons. Distributed along the axon and soma of the neurons.
Types of Voltage Gated Channels V oltage Gated Sodium Channels 9 members, responsible for membrane depolarization in action potential generation. Voltage Gated Calcium Channels 10 members, play an important role in both linking muscle excitation with contraction as well as neuronal excitation with transmitter release. Voltage Gated Potassium Channels 40members, role in repolarization of cell membrane after action potential
Transient receptor potential channels (TRP channels): 28 types, some of them are voltage gated, named after their role. Present in Drosophila phototransduction. Hyperpolarization-activated cyclic nucleotide-gated channel pacemaking channels in the heart, sensitive to cAMP, cGMP that alter the voltage sensitivity of the channels. Voltage sensitive proton channels helps in acid extrusion from cell, phagocytosis, strongly pH regulated.
Structure Several subunits with a central pore. Ion specific, but ions with similar charge and size can enter. Functionality governed by 3 main parts- the voltage sensor, the pore and the gate. Na, K and Ca channels have 4 transmembrane alpha subunits surrounding the pore. Six subunits: S1-S6. S1-S4: Voltage sensing region, S5-S6: Gate and pore. Regulatory beta subunits.
Mechanism For potassium channel: When a potential over the membrane, the associated electric field induces a conformational change in the potassium channel. The conformational change distorts the shape of the channel proteins sufficiently such that the cavity, or channel, opens to allow influx or efflux to occur across the membrane. difference is introduced
Voltage sensing in Na and Ca channels: Positive charges in the voltage sensing domain, presence of Arginine and histidine repeats in this segment. Gate acts as a mechanical obstruction to ion flow. Channel closes milliseconds after opening.
Ligand Gated Channels Group passing of several ions upon the binding of specific chemical messenger like neurotransmitters. of transmembrane ion channels that allow the Two Domains transmembrane domains including channel pore, Extracellular domain including ligand binding site. Function: Conversion of presynaptic chemical signal quickly and effectively into post-synaptic electrical signal. Three super families: cys-loop receptors , Ionotropic Glutamate Receptor, ATP Gated Channels
Cys-loop receptors Characteristic loop formed by a disulfide bond between two cysteine residues in the N terminal extracellular domain. Provides specificity for Acetyl Choline, Seratonin, Glycine, Glutatamate, -aminobutyric acid Structural elements are well conserved with a extracellular domain (ECD) harbouring an alpha-helix and 10 beta strands Following the ECD four transmembrane segments (TMSs) are present.
Ionotropic Glutamate Receptor Binds to Glutamate. Consists of a tetramer. Each terminal domain (ATD) which is involved in tetramer assembly, an extracellular ligand binding domain LBD, which binds glutamate, and a transmembrane domain TMD, which forms the ion channel. sub-unit consists of extracellular amino Each subunit of the tetramer has a binding site for glutamate formed by the two LBD.
ATP Gated channels Bind to ATP in order to open. They form trimers with two transmembrane helices per subunit and both the C and N termini on the intracellular side.
Cell communication Cell signaling is part of any communication process that governs basic activities of cells and coordinates all cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis. Errors in signaling interactions and cellular information processing are responsible for diseases such as cancer, autoimmunity, and diabetes. By understanding cell signaling, diseases may be treated more effectively and, theoretically, artificial tissues may be created.
Form of Signaling Cells communicate via various types of signaling that allow chemicals to travel to target sites in order to elicit a response. Paracrine signaling occurs between local cells where the signals elicit quick responses and last only a short amount of time due to the degradation of the paracrine ligands. Endocrine signaling occurs between distant cells and is mediated by hormones released from specific endocrine cells that travel to target cells, producing a slower, long-lasting response. Autocrine signals are produced by signaling cells that can also bind to the ligand that is released, which means the signaling cell and the target cell can be the same or a similar cell. Direct signaling can occur by transferring signaling molecules across gap junctions between neighboring cells.
Types of Molecules Intracellular receptors are located in the cytoplasm of the cell and are activated by hydrophobic ligand molecules that can pass through the plasma membrane. Cell-surface receptors bind to an external ligand molecule and convert an extracellular signal into an intracellular signal. Three general categories of cell-surface receptors include: ion -channel, G- protein, and enzyme -linked protein receptors. Ion channel -linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein, which then interacts with either an ion channel or an enzyme in the membrane. Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme.
Signaling Molecules Produced by signaling cells and the subsequent binding to receptors in target cells, ligands act as chemical signals that travel to the target cells to coordinate responses. The types of molecules that serve as ligands are incredibly varied and range from small proteins to small ions like calcium (Ca2+). Small Hydrophobic ligands Water Soluble ligands Other Ligands
Small Hydrophobic ligands Small hydrophobic ligands can directly diffuse through the plasma membrane and interact with internal receptors. Important members of this class of ligands are the steroid hormones. Steroids are lipids that have a hydrocarbon skeleton with four fused rings; different steroids have different functional groups attached to the carbon skeleton. Steroid hormones include the female sex hormone, estradiol, which is a type of estrogen; the male sex hormone, testosterone; and cholesterol, which is an important structural component of biological membranes and a precursor of steriod hormones. Other hydrophobic hormones include thyroid hormones and vitamin D. In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream.
Water-soluble ligands Water-soluble ligands are polar and, therefore, cannot pass through the plasma membrane unaided; sometimes, they are too large to pass through the membrane at all. Most water-soluble ligands bind to the extracellular domain of cell surface receptors. The binding of these ligands to these receptors results in a series of cellular changes. These water soluble ligands are quite diverse and include small molecules, peptides, and proteins.
Other Ligands Nitric oxide (NO) is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane; one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue. NO has a very short half-life; therefore, it only functions over short distances. Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart.
