Live Cone Snails

INTRODUCTION TO CONE SNAILS Venom duct dissected

Cone snails are slow moving gastropods that comes under the phylum mollusca are a
type of marine snails which propels itself with its muscular foot.
Clinical RNA Isolation Extraction (Solvent or Buffer)
These snails are of particular in interest to researchers because of the variety of
venoms it contain. Biochemistry
Total RNA content Protein TLC
HABITAT AND FEEDING HABIT Atlantic Ocean
Estimation
Cone snails live in many different environments in
the ocean, (West Atlantic, Indian and Pacific Onean)
HPLC
Cloning
but they cannot survive in fresh water. Pacific Indian
Ocean
SDS-PAGE
Ocean
GC-MS, NMR

Small droplet of this venom ION CHANNELS CONOTOXINS SOURCE CHAIN FUNCTION BINDING
They live in coral reefs or in AND LENGTH SITE
shallow sandy waters where they
causes a great damage to its
prey, and the same impressive RECEPTORS
will often bury themselves under
the sand. destructive power of venoms Acetylcholine Conus 13-15 Inhibits post Acetylcholine
Receptor A geographus amino acids
synaptic ligand gated
has been turned into a life
Cone snails are usually solitary and they stay in same location for most of its life Conus magus 2 region at ion channel
saving drugs. disulphide
neuromuscula
depending on its diet and other survival factors.
Cone snails are nocturnal i.e, they become active during night time and search for bonds. r junction
prey. Prey is detected using chemosensor organs such as the osphradium. The snail Sodium Conus 16-25 Inhibits the Voltage
crawls towards it, extends its proboscis, and upon contact with any soft part of the body Channel O geographus amino acids
influx of sensitive
fires a barbed harpoon-like modified radula into the prey.
Conus 3 sodium ions sodium
maemoreus disulphide
at muscular channel
Cone snails are carnivorous ANATOMY OF CONUS bonds and neuronal
and they feed 70% on worms
sodium
(vermivorous), 15% on molluscs Anal notch: where snail excretes solid
(molluscivorous) and 15% on channel
waste
fishes (piscivorous). Calcium Conus 24-30 Blocks calcium Voltage
channel geographus amino acids channels at gated
Conus magus 3 neuromuscula calcium
Outer lip: where new shell growth occurs
disulphide r junction channel
Inner lip: smooth, usually not patterned bonds
Potassium Conus 27 amino Inhibits the Voltage
channel purpurascens acids flow of sensitive
Aperture: opening from which snail potassium potassium
emerges ions channel
NMDA receptor Conantokins Conus 17-22 Inhibits Glutamate
PREDATORS OF CONUS geographus amino acids NMDA receptors in
Conus No receptors CNS
It is supposed that the columellar muscle, the
radiatus disulphide
one that the snail uses to retract back into its
shell, is paralysed when the snail is stung. If the bonds
snail cannot retract back into its shell, and
cannot tighten the columellar muscle, its OTHER CONOPEPTIDES
predator will be able to pull it out of its shell Contulakin G Conus geographus Developed for treating
and eat it.
post operative pain
2 Rho conotoxin Conus tulipa Act as reversible non-
1 competitive inhibitor of
-1 adrenergic
1.The proboscis, a long extendable tube, is used for hunting purposes.
Harpoons are loaded into the tube and propelled into their prey, injecting it receptors
with venom. The harpoons are modified teeth that are stored in the radular Chi conopeptides and Conus marmoreus Developed for
LIFE CYCLE OF CONUS sac. Each harpoon is filled with venom before being propelled from the snails conotoxins treatment of
proboscis into its prey. neuropathic pain
It is difficult to track
the entire natural life Contryphans Conus ventricosus May treat endocrine
2.The siphon, is similar to a nose. The snail uses it to detect its prey in the
cycle of a cone snail. Conus regius and neuronal disorders
surrounding waters. It is also a tool for respiration, directing water to the gills.
The female deposits
egg capsules under ION CHANNELS AS DRUG TARGETS
3.The eye stalks are located on either side of the mouth.
the sand, from which AND EMERGENCE OF CONOTOXINS
the young eventually FOR DRUG DEVELOPMENT
4.The mouth of the snail can be much extended to engulf its prey. A muscle is
emerge as swimming
contracted to bring the mouth back into the shell. Nerve cells are surrounded by a membrane that
larvae or miniature
adults. allows some ions to pass through ion channels, but
5.A long muscular foot extends to allow the snail to move along surfaces. The blocks the passage of others (a semi-permeable
columellar, or foot, muscle contracts to pull the foot in and close the aperture membrane).
The snail secretes chemicals that become its shell. (the opening) of the shell. The important signalling chemicals in the body are
The shell is mostly made of calcium carbonate, the
VENOM SYSTEM electrically charged: they are called ions.
same material found in egg shells and marble.
Venoms of cone snails are found to be a reservoir of
The snail secretes these chemicals as it grows so the
millions of bioactive peptides with highly diverse
shell continues to fit the body size of the snail at all stages
sequences and structures.
of its life.
These are having numerous clinical importances
because the ion channels are their main target for its
Adult function to emerge
Adults mate The most successful venomic project is the
Reproduction
development of PRIALT, the first conotoxin
derived drug.
This analgesic is a synthetic version of a
Sub-adult Egg laying conotoxin isolated from the venom of Conus
female magus.
The conus uses its venom system to produce and store the
The target of Zincotide is to inhibit the N
Postmetamorphic

venom and to prepare it for delivery.

Intracapsular

Venomous toxin components are produced in the venom duct, type calcium channel, which is involved in
growth

attached to the venom bulb. the pain pathway.

The venom bulb, a modified salivary gland, contracts to push
venom into the harpoons.
The harpoon is like a disposable, hypodermic needle.
Once a harpoon has been used, it is discarded. The snail reloads
Crawling Egg capsule another harpoon for its next attack.
Stage cluster
CONOTOXINS
Metamorphosis Planktonic
development
Conotoxins, rich in disulphide bonds are small peptides of 10 to
35 residues.
They have a high and specific effect on various receptors in pain
pathway, voltage gated ion channels and nerve transmission.
REFERENCES
Toxins present in the venom of the cone snails represent a
Alonso D, Khalil Z, Sathunanthan N & Livett B G, Drugs from the sea: valuable source of neuropharmacologically active peptides named
Conotoxins as drug leads for neuropathuc pain and other neurological as conotoxins.
conditions. Mini Reviews in Medicinal Chemistry, 3 (2003) 785-787.
Cone snails make neurotoxins (called conotoxins) that can affect
Caitriona Gunning & Ashley Chadwick. Cone Snails. University of Utah. many ion channels. Snail venom contains hundreds of different
Photos by Kerry Matz Olivera Lab, University of Utah.
conotoxins to ensure paralysis of prey.
Nicolas P & Mande H, The Terebridae and teretoxins: Combining Phylogeny
Once injected, the venom acts in different stages.
and anatomy for concerted discovery of bioactive compounds, BMC Chemical
Biology, 10 (2010) 7. The first is called the lightning strike. It immediately
immobilises the prey, which starts to jerk violently
Another is known as the motor cabal. The venom components
interfere with neuromuscular transmission.
Zincotide is adminstered in case of acute
and chronic pain caused by HIV, cancer,
post operative pain.
It has been found to be efficient in patients
who have no response to opioid drugs.
The only listed side effect is hypotension,
and this may be due to the block caused by
the drug prialt on neurons of calcium
channels that regulate the blood pressure.
There are other conotoxin derived peptides that have
been reached clinical trials at various stages. (i).
Contulakin G neurotensin receptor, (ii). MrIA
norepinephrine receptor, (iii). Vc1.1 nicotinic
receptor, (iv). Conantokin G NMDA receptor, (v).
PVIIA potassium channel, (vi). O MrVIB
Sodium channel. These conotoxins have potential
therapeutic for pain but they are being evaluated for
epilepsy or myocardial infarctions
CONCLUSION
Poison kills the poison, the famous proverb has been
the underlying basis for the researchers in finding the
novel bioactive metabolites from living organisms.
The drugs obtained from the conotoxins are found to
be neurologically active as it reveals the complexity of
voltage gated and ligand gated ion channels. Thus venom
peptides remain as an untapped source of new probes for
research and leads to novel therapeutics.