The document is a presentation on ligand gated ion channel receptors. It discusses the molecular structure and organization of GABA-A receptors, which are pentameric and composed of various subunit combinations. It describes the mechanism of action of GABA-A receptors, where binding of GABA opens a chloride channel, allowing chloride ions to flow into the cell and cause hyperpolarization. It also briefly mentions voltage operated channels and their role in membrane excitability.

1. Assam Downtown University
Panikhaiti, Guwahati –
781026, Assam, India
2021
TOPIC ON LIGAND GATED ION CHANNEL RECEPTOR
Presented By
DIXHU RAJ DIXIT
M.Pharm Pharmacology 1st semester
Enrollment-ADTU/2021-23/MPS/007
Submitted To
Dr. Partha Pratim Dutta
Associate Professor, Faculty of Pharmaceutical Science, Adtu

2.  Introduction
 Molecular Structure and Organization of ligand gated ion
channel Receptor
 Mechanism of Action
 Voltage operated Channel
 Conclusion
Content

3. What is Receptor?
 Receptor is a macro-molecular protein on the cell
membrane or within the cytoplasm or cells nucleus
that binds to a specific factor (ligand). Such as a
neurotransmitter, hormone or other substance and
initiates the cellular response to the ligand.
 They form the sensing elements in the system of
chemical communications.Types of receptors a)
Ionotropic or channel linked receptorreceptor b)
Enzyme linked receptor c) G-protein coupled receptor
d) Nuclear receptor.

5. INTRODUCTION
 The ligand-gated ion channels are also known as
ionotropic receptors. These are membrane proteins with a
similar structure to other ion channels but incorporating a
ligand-binding (receptor) site, usually in the extracellular
domain.Examples : Nicotinic acetylcholine receptor,
Glutamate receptor etc.
 Ligand gated ion channel selectively permeable to chloride
ion that means it enclosing the chloride ion channel.
 Ligand gated ion channel are cell membrane receptor.
 Ligand gated ion channel receptor enclosed different types
of ion channel cl ion channel Na etc.
 Depending upon the Na, Cl channel ion nature of these ion
may produced excitation function or inhibitory function.

7. Molecular Structure and
Organization of GABAA Receptor
 It is a pentameric in nature.
 It is composed of 5 subunit . 5 subunit contain total 19
different subunit.
 Ligand gated chloride channel receptor.
 Cys- loop receptor / cys- loop super family. Cys is a ligand
gated ion channel which is present in the Membrane.
 Main adult isoform of GABA-A is composed of gamma2,
beta2, alpha1, beta2 and alpha 1(Counterclock wise around
central pore)
 90% of GABAA receptor contain gamma subunit. But Delta
subunit can substituted with Gamma.
 GABAA receptor abundant into the thalamus,
hypothalamus and Hippocampus.

8.  Generally ligand gated ion channel receptor 3 types of
super family are-1. Cys –loop receptor 5% 2.Ionotropic
glutamate receptor, 3.ATP gated receptor (P2x).
 GABA A receptor subunit are primarily arranged into
four clusters on the human genome chromosomes are-
1. Alpha2, Alpha 4,Beta1 and Gamma 1-Gene
chromosomes 4.
2.Alpha1, alpha6, Beta2 and Gamma 2-Gene
chromosome 5.
3.Alpha 5 , beta 3 and Gamma 3 –Gene chromosomes 15.
4.Alpha 3,Epsilon and Tetta Genes on chromosome X.

10. MECHANISM OF ACTION
 Ligand gated ion channel receptor GABA it will come Bind
with specific site, When the GABA bind with GABA A the
chloride channel open.
 Binding site of GABA in a GABA A receptor is Alpha and
beta. Benzodizepine bind with Alpha and gamma and
Barbiturate bind with Alpha and Beta.
 GABA bind in the Alpha, Beta and gamma subunits.
 When chloride channel open the chloride ion come inside.
 Concentration of cl ion it is more into the extracellular side
compound to the intracellular side.
 When the sodium ion is open sodium will come inside it
will cause the depolarization Or excitement. Where as
chloride ion is abundant into extracellular site.

11.  When the cl ion inside membrane potential goes
down(hyperpolarization)
 Membrane potential Reduce.hyperpolarization
nothing but the inhibition.
 Mature subunit composed of ~450 Amino acid residue.
 Each subunit contain- 4 Hydrophobic transmembrane
domains(TM1-TM4)
 N- terminal ( Interects with a variety of drugs).
 One small extracellular C terminus.
 One short intracellular loop that links TM1 and TM2.

12.  One short extracellular loop-that links TM2 and TM3.
 One long intracellular loop that links TM3 and TM4.
Can be modulated by phosphorylation site of protein
interection and postrasiational modification modulate
receptor activity.
 TM2 is believed to form the pore of the chloride
channel.
 TM2 of each subunit forms a selective pore that is
permeable for the chloride ion passage.
 Total no of transmembrane domains- 20.

13.  Each subunit spans the membrane four times, so the channel
comprises no less than 20 membrane-spanning helices surrounding a
central pore.
 One of the transmembrane helices (M2) from each of the five subunits
forms the lining of the ion channel.
 The five M2 helices that form the pore are sharply kinked inwards
halfway through the membrane, forming a constriction, and are
believed to swivel out of the way when acetylcholine is bound, thus
opening the channel
 The use of site-directed mutagenesis, which enables short regions or
single residues of the amino acid sequence to be altered, has shown
that a mutation of a critical residue in the M2 helix changes the
channel from being cation selective (hence excitatory, in the context of
synaptic function) to being anion selective (typical of receptors for
inhibitory transmitters, such as GABA) Other mutations affect
properties such as gating and desensitisation of ligand-gated channels

15. Voltage operated Channel
 When The cell membrane is depolarized The
mechanism of membrane Excitability.
 Activation induced By membrane depolarisation is
short lasting even if the depolarisation is
maintained.
 The most important channel in this group are
selective Sodium potasium and calcium channel.

17. Conclusion
 GABAa is classified as a ligand-gated ion
channel/inotropic receptor. GABAa is considered in
fast synaptic inhibition. Upon the receptor binding to
GABA, an ion pore opens to allow chloride to move
across the cell membrane. Chloride is a negatively
charged ion and will follow into the area of positive
charge. Typically, chloride will flow into the
intracellular space. The addition of negative charge
will decrease the resting potential of the cell, thus
causing an inhibitory effect. GABAa receptors are
located throughout the central nervous system.

18. Reference
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