This document discusses different types of ion channels. It begins by describing the general structure and function of ion channels. It then classifies ion channels into three main categories: voltage-operated channels, receptor-operated channels, and second messenger-operated channels. For each category, it provides details on molecular structure, mechanism of gating or activation, examples, and biological roles. It also discusses abnormalities that can result from mutations in some voltage-operated channels.

1. BY:
T.ANANTHAKUMR
REGNO.BMS14312

2. Topic :
Voltage operated channel
Receptor Operated Channel
Second messenger operated channel

3. Ion channel
Ion channels are pore-forming membrane
proteins whose function is establishing a
resting membrane potential, shaping action
potentials and other electrical signals by
gating the flow of ions across the cell
membrane, controlling the flow of ions across
membranes, and regulating cell volume.

4. Cont….
Highly selective in type of ion transported
Very high rate of ion transfer.
Ions are transported across electrochemical
gradient.
Passive mechanism.

5. 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

7. Classification based on gating
1
• Voltage operated Ion
Channels
2
• Receptor operated Ion
Channels
3
• Secondary messenger
operated ion channels

8. Voltage operated channel
 A class of transmembrane proteins that
form ion channels
 Activated by changes in the
electrical membrane potential near the
channel
 Voltage-gated ion-channels are usually ion-
specific, and channels specific
to sodium (Na+), potassium (K+), calcium (Ca
2+), and chloride (Cl–) ions

10. Structure and Function
Voltage-dependent channels are
made of three basic parts:
Voltage sensor
The pore or conducting
pathway and
Selectivity filter

11. Cont….
Voltage gated ion channels consist of a highly
processed
α subunit, associated with
auxiliary β subunits.
The pore-forming α subunit is sufficient for
functional expression, but the kinetics and
voltage dependence of channel gating are
modified by the β subunits

12.  The α subunits are organized in four
homologous domains (I-IV) each with six
transmembrane segments (S1-S6) - 24
transmembrane segments in total. The pore
forming segments are formed by S5 and S6.

13. Each of these segments
coils is called a
transmembrane
domain, and within
a transmembrane
domain the side chains
necessarily face outward
where they readily
interact with the
lipids of the membrane are known as
Polypeptide chain.

14. Channel structure
Voltage
Gated
Channels
Domains TM
Segment
s
Sub-
Units
Pore
Forming
Regions
Voltage
Sensor
V.G Na+ 4 6 1 S5-S6 S4
V.G Ca2+ 4 6 4 S5-S6 S4
V.G Cl- 4 6 4 S5-S6 S4
V.G K+ 4 6 1 S5-S6 S4

15. A single transmembrane domain is shown as
the voltage sensor that operates the gate.
The S4 segment of voltage gated
channel is the voltage
sensor that is responsible
for changing conformation
as the voltage changes.
All voltage gated channels
have this S4 segment

16.  Changes in the membrane potential modulate the
channel's opening or closing, as changing the
membrane potential changes the relative amounts of
positive and negative charges on the inside and
outside of the membrane. Like charges repel, so the
positively charged S4 segment
will be pushed away from
a positive intracellular fluid
towards the negative extra
cellular fluid, changing the
protein's conformation and
opening the channel.

17. Voltage-gated ion channels
 Involved in:
1.Initiation and propagation of action
potentials
2. Control of synaptic transmission
3.Intracellular ion homeostasis
4.Other aspects of intracellular function
 Acting as activators of intracellular enzymes
 Coordinating signals between cell membrane
and internal organelles (e.g., mitochondria).

18. At a typical resting membrane potential (for
example, -70 mV) the channel is closed. Then
should any factor depolarize the
membrane potential
sufficiently (for example,
to -50 mV), the voltage
sensor moves outward
and the gate opens.
The channel can also
close (deactivate) by negative voltages that
restore the down position of S4 and close the
gate.

20. Mutated VOC’s
 Mutations within these VOCs can lead to a
variety of inherited diseases known
collectively as channelopathies:
• Episodic ataxia type 2
• Familial hemiplegic migraine (FHM)
• Spinocerebellar ataxia type 6 (SCA6)
• Spinocerebellar ataxia type 12 (SCA12)
• Timothy syndrome..etc,.

21. Receptor operated channel
 Also commonly referred as ionotropic
receptors
 A group of transmembrane ion channel proteins
which open to allow ions such as Na+, K+, Ca2+,
and/or Cl− to pass through the membrane in
response to the binding of a chemical
messenger such as a neurotransmitter.
 Involved mainly in fast synaptic transmission.
 Eg: nAchR, GABAA, and glutamate receptors of
the NMDA, AMPA and kainate types.

22. Molecular Structure
 ligand binding site in extracellular domain.
 4 subunits α, β, γ and δ.
 α2, β, γ - pentameric str
- 2 ligand binding sites
 Each subunit spans
the membrane 4 times;
all subunits form a central
pore. Ligand binding site

23. Structure of ROC’s

24. These proteins are typically
composed of at least two different
domains:
• includes the
ion pore
A
transmembrane
domain
• includes the
ligand binding
location
An extracellular
domain

26. Classification
There are three main groups of ROCs
Cysteine-loop receptors
 Nicotinic acetylcholine receptors (nAChRs)
 5-Hydroxytryptamine 3 (5-HT3) receptors
 γ-Aminobutyric acid (GABA) receptors
 Glycine receptors (GlyRs)
 Glutamate receptors
 α-Amino-3-hydroxy-5-methylisoxazole-4-
propionic
acid (AMPA) receptors
 N-methyl-D-aspartate (NMDA) receptors
 Kainate receptors
ATP-sensitive P2X receptors

28. Second messenger-operated
channels (SMOCs)
 There are a number of second messenger-
operated channels(SMOCs) that are
controlled by messengers coming from inside
the cell
 Eg:the cyclic nucleotide-gated channels
(CNGCs), the arachidonic acid-
regulatedCa2+ (ARC) channel and the
diacylglycerol (DAG)

29. Mechanism of SMOC’s

30. Cyclic nucleotide-gated channels
(CNGCs)
 Conduct Ca2+ and to a lesser extent, Na+
 Play important role in sensory transduction
of visual, olfactory and gustatory signals
 Also expressed in other cell types within the
brain, testis and kidney
 There are six mammalian CNGC genes

31. CNGC
CNGA
CNGA1--CNGA3
subunits
form channels
CNGA4 subunit
have a more
modulatory
function
CNGB
two CNGB subunits
have a more
modulatory
function

32. Sensory function of CNGC
The CNGCs are particularly important in the
function of a number of sensory cells:
• In retinal rods, the channel is composed of a
heterotetramer containing three CNGA1
subunits and one CNGB1 subunit. The channel
responds to cyclic GMP to maintain the dark
current
• In olfactory cilia, the channel has two CNGA2
subunits , one CNGA4 subunit and one CNGB1b
subunit. The channel opens in response to
cyclicAMP formed during transduction of
olfactory stimuli

33. Abnormality
Retinitis pigmentosa carry mutations in
CNGA1 and CNGB1.
 Achromatopsia (colour blindness)
is caused by loss of CNGA3 and CNGB3.