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Thursday, August 16, 2012
Smelling the Potassium
We seem to be pinning down the chemical activators of our vestigial
instinctual behavior drivers. I am not sure were this will take us,
but I suspect that we will ultimately engineer perfumes that allow us
to play with lust and aggression onn demand. That is hardly a bad
thing be ause what comes with that is the learned discipline needed
to control the effects.
Once a person understands that these emotions are induced he or she
can stop attempting to rationalize them and recognize them for what
We sort of know that they are there but they are also normally quite
subtle and easily sneak up on one. Now we may begin to break out the
Smell the potassium
by Staff Writers
Kansas City MO
(SPX) Aug 02, 2012
In an unexpected
finding, Ron Yu and his team revealed that potassium channels
contribute to the primary activation of the vomeronasal organ, which
detects pheromones. Credit: Illustration: Courtesy of Dr. Ron Yu,
Stowers Institute for Medical Research.
The vomeronasal organ
(VNO) is one of evolution's most direct enforcers. From its niche
within the nose in most land-based vertebrates, it detects
pheromones and triggers corresponding basic-instinct behaviors, from
compulsive mating to male-on-male death matches.
A new study from the
Stowers Institute for Medical Research, published online in Nature
Neuroscience extends the scientific understanding of how pheromones
activate the VNO, and has implications for sensory transduction
experiments in other fields.
"We found two new
ion channels-both of them potassium channels-through which VNO
neurons are activated in mice," says Associate Investigator C.
Ron Yu, Ph.D., senior author of the study. "This is quite
unusual; potassium channels normally don't play a direct role in the
activation of sensory neurons."
shrunken, seemingly vestigial VNOs, but still exhibit instinctive,
pre-programmed behaviors relating to reproduction and aggression.
Scientists hope that an understanding of how the VNO works in mice
and other lower mammals will provide clues to how these innate
behaviors are triggered in humans.
The VNO works in much
the same way as the main olfactory organ that provides the sense of
smell. Its neurons and their input stalks, known as dendrites, are
studded with specialized receptors that can be activated by contact
with specific messenger-chemicals called pheromones, found mostly in
When activated, VNO
receptors cause adjacent ion channels to open or close allowing ions
to flood into or out of a neuron. These inflows and outflows of
electric charge create voltage surges that can activate a VNO neuron,
so that it signals to the brain to turn on a specific behavior.
In 2002, as a
postdoctoral researcher at Columbia University, Yu was a member of
one of the first teams to find that VNO receptors rely heavily on a
calcium channel called TRPC2.
But there were hints
that VNO neurons use other ion channels too; and in a study reported
last November in Nature Communications, Yu's team at Stowers,
including first author SangSeong Kim, Ph.D., a postdoctoral
researcher, found evidence for the role of a chloride-specific
In the new study, Yu,
Kim and their colleagues looked for VNO potassium channels, which
admit positively charged potassium ions. They began by setting up
whole-cell patch clamp tests, in which tiny electrodes measure the
net flow of charged ions through the membranes of neurons in a slice
of mouse VNO tissue.
To determine the
contribution of potassium ions to these currents, they replaced the
potassium ions in the neurons with chemically similar cesium ions,
which cannot get through potassium channels.
potassium-depleted VNO neurons were exposed to pheromone-containing
mouse urine, the usual net inward flow of positive charge was
significantly greater than it had been when the neurons contained
That and other
experiments with the VNO tissue slices suggested that potassium ions
normally flow out of VNO neurons through potassium channels when a
VNO receptor is activated.
This was not
completely unexpected; neurons typically have a greater concentration
of potassium ions inside than outside, leading to an outward flow
when potassium channels are opened. The outward flow originates
mostly from the main bodies of neurons and helps reset neurons to a
resting state voltage.
However, in the VNO
neurons a strong outward flow of potassium also occurred within the
dendrites, directly countering the inward flow of positive ions that
would activate the neurons. "It seemed a bit bizarre that such
an important system would work against itself in this way," Yu
The team was able to
zero in on the two potassium channels responsible, which are known as
SK3 and GIRK.
But when they set up
experiments to evaluate these channels not in VNO tissue slices but
"in vivo"-in the working VNOs of live mice-they found a
very different result: On balance the potassium channels now sent
potassium ions in the inward direction. In fact, these two newly
discovered channels seemed to account for more than half of the
inflowing-potassium phenomenon is known to occur in another type of
sensory neuron, the sound-sensitive cochlear hair cell, whose
external environment contains relatively high levels of potassium.
"This made us wonder whether the VNO also has a high level of
potassium in the fluid surrounding its dendrites," says Kim.
It does. It turns out
that the standard preparation of tissue slices for the initial
patch-clamp experiments had washed away that naturally high
The resulting low
concentration had misleadingly caused potassium ions to be sucked out
of VNO neuron dendrites when the SK3 and GIRK potassium channels were
opened. "It's a cautionary tale that shows the importance of
doing in vivo experiments," Yu says.
The finding that
potassium channels contribute to the primary activation of the VNO
could be a clue to the origins of the organ.
that the VNO may have evolved to have a high extracellular
concentration of ions, as well as multiple ion channels, so that it
remains functional even when it comes into contact with various
ion-rich bodily fluids," Yu says. "The diversity of
signaling pathways perhaps make it more robust in triggering innate
Other researchers who
contributed to the research include Limei Ma, Ph.D. and Kristi L.
Jensen, of Yu's laboratory at the Stowers Institute; Michelle M. Kim,
Ph.D., of Columbia University; and Chris T. Bond, Ph.D., and John P.
Adelman, Ph.D., of Oregon Health and Science University.