Biology concepts – thermoregulation, heat sensing, TRPV1,
evolution, neurotransmitters, birds, ectothermy, diet-induced thermogenesis
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BBC
television has a very nice Sherlock Holmes show
running
nowadays, but it has ticked off some mental
health
professionals. Sherlock describes himself as a
high
functioning sociopath. I have read several angry
letters
from those in the profession saying that he
should
stop doing so, he is using a mental disorder as
an
excuse for just plain rude behavior.
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There is an argument currently raging as to whether there is
any difference between these two labels for anti-social personality disorder.
The major similarity is in self-centered actions without remorse for doing
wrong to others. The differences may lay in organization. Psychopaths are
impulsive while sociopaths may plan things out and use charm to conceal
themselves. Others say psychopathy is genetic and sociopathy is learned. But
both groups are fine with breaking rules.
This blog has used rule breakers as models for explaining
biology concepts, just as medicine uses them as ways to find corrections for
when things go wrong. If one animal could be the poster child for rule breaking
in biology, it would have to be the naked
mole rat (Heterocephalus glaber).
There are so many rules that this animal breaks or ignores, it makes one wonder
if it's a sociopath or a psychopath.
In truth, the naked mole rat has no motivation for breaking
rules. It’s merely a reflection of the evolutionary forces that its ancestors
felt, adaptations to pressures over a long period of time. If rules had to be
broken, so be it. It’s evolution that’s the psychopath.
The broken rules we are concerned with in this post relate
to TRPV1. The capsaicin of chili peppers does not inflict pain on naked mole rats! H. glaber TRPV1 binds capsaicin just
fine, it just doesn’t result in pain. The difference comes in the spinal cord.
A 2008 paper shows that the connections from the TRPV1 expressing nociceptive
neurons to those neurons that would convey the signal to the brain are
different in naked mole rats, and the additional pathways result in a loss of
the pain signal.
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This
isn’t just a pile of naked mole rats that someone
dumped
out of a bucket. This is how they sleep. They
use
each other to keep warm because they are cold
blooded.
A cold-blooded mammal? Well, I never
imagined.
But they break more rules – they live much
longer
than other mammals, they don’t get cancer,
and
they have a queen like in bee hives. Drum roll
please
– the naked mole rat was named the vertebrate
of
the year for 2013 by Science
magazine.
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One of those other TRPV1 activators is acid. We said that a
pH below 5.5 activates TRPV1 and a pH between 5.5 and 6.5 makes TRPV1 more
sensitive. This is pertinent for naked mole rats because they live entirely
below ground. Their tunnels are high in CO2 from all their
exhalations. Excess CO2 in the tissues causes an acidosis, a low pH
situation. If the H. glaber TRPV1
acted as it does in every other mammal, then naked mole rats would be in
constant pain.
New research (2011) shows that the acid does indeed make naked mole rat
TRPV1 channels open just as capsaicin does, but the neurons don’t fire. Acid
suppresses a certain sodium channel downstream of TRPV1. Normally, the calcium
influx mediated by TRPV1 activates the Nav1.7 sodium channel, and
the neuron is depolarized and fires. But acid destabilizes the Nav1.7
channel and there is reduced firing.
This suppression occurs in all mammals, but it is a much
stronger suppression in naked mole rats, because two amino acids are changed in
their version of Nav1.7. Now we have two TRPV1 activators (capsaicin and acid) that no
longer result in pain, but for two different reasons. Is there more?
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Substance
P is a neurotransmitter and modulator
that
is important for pain signaling, but it also works
in
vomit regulation. In the medulla of the brain lies
the
vomit center, and it uses substance P to induce a
reversal
of the motion of the GI muscles that usually
moves
food through the GI tract. A spike of substance
P
in the wrong place, and here comes supper for a
return
engagement.
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But the question remains, did the mutations in TRPV1
signaling permit H. glaber to move
permanently underground, or did living underground put pressure on the naked
mole rat to adapt through TRPV1 mutations? It’s hard to tell which was the cart
and which was the horse.
The naked mole rat’s lack of pain signaling via TRPV1 may
help us humans. The more we know about the mechanisms of H. glaber TRPV1 action, the better we can design pain killers for
ourselves. Exceptions can often be our savior.
Another rule that naked mole rats break is that they are cold-blooded (ectothermic) mammals.
We know that TRPV1 is important in heat sensing, so does having altered TRPV1
pathways mean that the naked mole rat can’t thermoregulate and that’s why it’s
ectothermic?
The rats can still probably sense heat. Remember that there are
other TRPV proteins that are important in heat sensing; nothing says these
aren’t functioning just fine. For that matter, there is no evidence that the
TRPV1 of H. glaber is defective in
heat sensing. It just doesn’t result in a pain sensation.
And it would be wrong to believe that ectotherms don’t need
to sense heat. It may be even more crucial for ectotherms. Cold-blooded animals
must find the heat in their environment and soak it in – but not too much. This
means they must be experts at knowing how much heat they have and where they
can find more.
Ectotherms also need to know where the shade is, so they
can cool off if they get too hot. To prove this, we know that reptiles with mutated
thermosensors don’t shuttle between warmer and cooler areas and can’t maintain
a satisfactory physiologic temperature.
As weird as the naked mole rat is, birds also seem to break
the rules when it comes to TRPV1; they can order their food spicy as well. Why
is it significant that birds don’t sense capsaicin as burning pain? Remember that chilies are a group of plants with fruits. Those plants have evolved capsaicin to inhibit
herbivorous predators and fungal infections, as we talked about last week. Now we have the fact that birds don’t react to capsaicin. How are these linked?
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Squirrels
are the bane of every backyard birder’s
existence.
They eat ten times as much feed as the
birds,
and they can find some creative ways to
reach
the bird food. Try adding pepper flakes to
the
bird feed, squirrels feel the burn, but your
song
bird visitors won’t.
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The TRPV1 of most birds doesn’t have a vanilloid binding
site. The channels work for heat sensing and do react to acids, but there is no
activation by capsaicin. Since there is no capsaicin binding site, birds only
taste the peppers, they don’t get the burn. It's possible that they taste the
many different vanilloid compounds, so peppers may taste a little like vanilla
to birds.
I still have one question – there's certainly a
reproductive advantage for peppers when birds don’t sense capsaicin (for seed
dispersal), but where is the advantage for birds? And how could pepper plants
force the evolution of a different TRPV1 in birds? One possibility - maybe birds
evolved a different TRPV1 to take advantage of a food source that other animals
avoid. No competition for food would definitely be a reproductive advantage for
birds.
But this explanation has exceptions as well. The TRPV1 of
chickens is activated by capsaicin.
It is weak, taking 3-4 times more capsaicin to get a reaction, but it does work.
So if you own chickens, don’t give them very spicy feed. Ducks on the other
hand, have a TRPV1 that doesn’t sense capsaicin or heat.
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Some
foods are considered negative calorie items. They
supposedly
cost more to digest than the energy they
provide
in calories. I’m not sure if I believe that all these
foods
are negative calorie foods. If they were, there would
be
a lot of starving vegetarians. If not dead, they would be
awfully
weak and tired.
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So thermosensing must be important. Even in most animals
that don’t respond to capsaicin, their TRPV1 still works in thermoregulation. I
can give you an idea of how intricate and detailed this thermoregulatory system
is by talking about digesting spicy food. Your body uses energy and metabolism to
digest the food you eat. This energy use produces heat as a byproduct, and
warms you up a bit. This is called diet-induced
thermogenesis. Celery is an excellent diet food because the energy you use
to digest it is the same or more than the calories in the celery itself.
For some reason, spicy foods increase diet-induced
thermogenesis; you expend more energy and heat up more when eating spicy foods than when eating the
same foods without the capsaicin. Recent evidence indicates that including
capsaicin and medium chain triglycerides in a meal will increase diet-induced
thermogenesis by over 50%. This combination also makes you feel full sooner and
therefore decreases overall caloric intake.
The spice also makes you use more energy for digestion, but
it also makes your body think it is warmer than it is, so it tries to cool
down. Cooling down also takes energy, so eating spicy food really does burn
more calories - maybe because fat takes more energy to digest and capsaicin is
a lipid-like molecule.
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Some
weird products include capsaicin for the supposed health
benefits.
Here are capsaicin drinks. Including capsaicin in a diet
will
help you eat less, but I am thinking it may be because you
just
get tired of sweating and feeling like your mouth is on fire.
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Next week we'll see that TRPV1 is even more amazing. Not
every spicy food contains capsaicin, there’s mustard, black pepper,
horseradish, ginger, cinnamon, etc. Some of these even make your capsaicin seem
spicier.
For
more information or classroom activities, see:
Naked
mole rat –
Substance
P –
Seed
dispersal –
Diet-induced
thermogenesis -
