Presented By:
Lyric Bowles
Mizba Kesani
Kisa King
The Poison Dart Frog
 Kingdom: Animalia
 Phylum: Chordata
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Class: Amphibia
 Order: Anura
 Suborder: Neobatrachia
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Family: Dendrobatidae
The Poison Dart Frog
Habitat: native to the humid, tropical
environments of Central and South America; found
mostly in the rainforests of Columbia
Temperature: 22 -27 oC (high) - 16-18 oC (low)
Humidity: 80-100%
Size: up to 2.5 inches
Weight: up to 2 grams
Life Span:
Captivity: up to 25 years
Wild: approximately 1-3 years
Diet: small insects and other small invertebrates
The Poison Dart Frog
These frogs are brightly colored in aposmatic patterns to
warn predators of their toxicity.
Females compete for "nests" and males compete for the best
spot from which to broadcast their mating calls
Females often lay their eggs on the forest floor or on leaves.
Adult frogs produce mucous which functions as a “glue” and
allows tadpoles to be transported to an aquatic environment
on the backs of their parents.
While in the water, tadpoles diet consists of small
invertebrates; however, the mother is known to deposit eggs
into the water in order to supplement the tadpole's diet.
The Poison Dart Frog
Some species, three in particular, are extremely toxic to
humans. The most poisonous of the three is the golden
poison dart frog (Phyllobates terribilis).
A single golden poison dart frog can kill between 10-20
people (or other large mammals); this is equivalent to
approximately 10,000 mice!
Local indigenous tribes of Central and South America use
the toxin produced from P. terribilis in the darts which they
use for hunting. Once on the dart, the toxins can keep its
effect for over 2 years.
 The Golden Poison Dart Frog is currently thought to be the
most poisonous vertebrate!
Toxin
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Batrachotoxin (BTX) is the actual
compound secreted by the
poison dart frog.
BTX was first discovered in the skin secretion of the Columbian
poisonous dart frog in the 1960s.
The structure of this toxin is shown to be a steroidal alkaloid.
Studies have shown that this toxin is not produced by these frogs
while in captivity. Therefore, it has been theorized that part of the
toxin is produced by consumption of certain foods available to frogs.
A study conducted in 2004 showed that this toxin comes from the
consumption of choresine beetles by these frogs. However, choresine
beetles also cannot produce parts of this toxin, so to do so, they eat
different types of sterol producing plants.
(Choresine bettle)
Toxicity
•
BTX is a powerful neurotoxin with a low LD50 of 2 g/kg in
mice and 1-2 micrograms/kg in humans.
•
The lethal dose for a 150 pound human is about 100
micrograms, which is equivalent to the weight of two
grains of table salt!
•
BTX is fifteen times more poisonous than Curare (another
arrow poison used by South American Indians; obtained
from plants).
•
Batrachotoxin is ten times more poisonous than
tetrodotoxin (toxin produced by puffer fish).
•
BTX also has dangerous affects on the heart similar to
those of digitalis.
Mechanism of Action
Batrachotoxin works by changing the membrane
potential of a cell. This results in the numbing of human
muscular tissues.
• The membrane potential is the voltage difference between
the outside and inside of the cell (ion concentration
between inside and outside of cell).
• A normal cell has a higher concentration of potassium
ions inside the cell and higher concentration of sodium
outside the cell.
• The ion concentration between the exterior and interior
cell is maintained by ion channels and ion pumps.
•
How does batrochotoxin affect the
membrane potential?
Batrachotoxin binds to the voltage-gated sodium channel
of the cell membrane.
• This binding causes the sodium channel stay permanently
open. The open conformation allows ions to freely pass
through the membrane which changes the membrane
potential.
• The change in membrane potential and the loss of the
sodium/potassium concentration gradient keeps nerve
and muscle cells from transmitting electrical signals
properly and from carrying on their natural functions.
• This leads to paralysis and death, with death resulting
from muscular and respiratory paralysis.
•
Treatment
•
This toxin can be can be treated with local anesthetics,
anti-arrythimic drugs, anti-convulsants, and tetrodotoxin.
•
These treatments keep batrachotoxin from binding to the
voltage-gated sodium ion channels.
•
Local anesthetics may act as receptor antagonists or as
competitive antagonists, which block the action all
together.
•
Tetrodotoxin is a noncompetitive inhibitor that binds to
voltage-gated sodium ion channels (similar to
batrachotoxin), but instead of permanently opening the
channels, it closes them.
Treatment
 There is currently no known antidote for batrachotoxin
poisoning!
 Like veratridine, aconitine and grayanotoxin,
batrachotoxin is a lipid-soluble poison which alters the
ion selectivity of sodium channels. This suggests a similar
site of action amongst these toxins. Based on this
similarity, researchers are attempting to obtain a
treatment for batrachotoxin poisoning by
modeling it after treatment for these other poisons.
 As mentioned earlier, membrane depolarization caused
by BTX can be prevented or reversed by either
tetrodotoxin or saxitoxin, but this is not an antitode and
side effects can be severe.
Present/Future Medical Uses
 In recent years, researchers have found that poison dart
frog batrochotoxins are actually 1000 times more effective
than morphine at treating pain!
 More importantly, unlike morphine and other painkillers,
there are no addictive properties associated with BTX.
 BTX could potentially become an active ingredient in
painkiller ointments.
 In 1998, scientist were able to synthesize BTX in the laboratory
and have done extensive research regarding structure and
function of BTX, as well as, its interaction with voltage-gated
sodium channels.
The Bigger Picture
 Frogs have existed on Earth for more than 250 million
years; surviving dinosaurs, asteroids and ice ages.
 Today, however, more than 1/3 of the all amphibian
species are in decline and/or are on the verge of
extinction.
 The main contributor to this decline is the invasion of
Chytridiomycosis.
(Frog population infected with
Chytridiomycosis)
The Bigger Picture
 Chytridiomycosis is a disease caused by an aquatic
chytrid fungal pathogen known as Batrachochytrium
dendrobatidis (BD).
 Chytridiomycosis attacks the skin of frogs depriving
them of oxygen and ultimately leads to death.
 Researchers have no idea where this pathogen
originated or how to contain it once it arrives at a frog
population.
 Why is this significant?
The Bigger Picture
 Researchers have only begun to study the beneficial
properties of secretions obtained from the skin of frogs.
With populations in decline, there is no telling what
medical discoveries will disappear with them!
 These little creatures could hold the key to solving
numerous medical dilemmas and they could all be gone
before we have a chance to utilize and understand them
fully.
 Batrochotoxins are not the only toxin being researched for
its medical uses. Chemicals secreted through the skin of
frogs are being research for everything from treatment of
infections to treatment of HIV.
Take Home Message
 Batrachotoxin is a neurotoxin secreted through the skin of
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poison dart frogs. It is because of this toxin that the Golden
Poison Dart Frog has been called the most poisonous vertebrate.
Batrachotoxin works by permanently opening voltage-gated
sodium channels that are essential to the proper functioning of
the nervous system.
Batrachotoxin has been used by several tribes for hunting
purposes. It is being researched for its benefits in treating pain.
There is no known antidote for batrachotoxin poisoning but
treatments are available.
Finally, with amphibian populations slipping away faster than
scientists can study them, there is no telling what other
medically significant toxins will go undiscovered.
References
 Myers, C. W., J. W. Daly, and B. Malkin (1978). "A dangerously toxic
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new frog (Phyllobates) used by Embera Indians of western Colombia,
with discussion of blowgun fabrication and dart poisoning". Bull. Amer.
Mus. Nat. Hist. 161 (2): 307–366.
Caldwell, J.P. (1996). "The evolution of myrmecophagy and its
correlates in poison frogs (Family Dendrobatidae).". Journal of Zoology
240: 75–101.
"AmphibiaWeb - Dendrobatidae". AmphibiaWeb.
http://amphibiaweb.org/lists/Dendrobatidae.shtml. Retrieved 2010-0310
“Batrachotoxin”.
http://chemweb.calpoly.edu/cbailey/377/PapersW08/PaulM/index.ht
ml. Retrieved 2010-04-05
“Chytrid Fungus-What is chytridiomycosis?”. Chytrid Fungus.
http://web.me.com/vancevredenburg/Vances_site/chytridiomycosis.ht
ml Retrieved 2010-03-15
“Batrachotoxin” http://www.wou.edu/~hgrimes/ch350/. Retrieved
2010-03-10