A cellular "porthole" known best for its role in the
digestive system apparently has a major role in helping the
brain sense odors, Johns Hopkins scientists report in the
Feb. 17 issue of Neuron. The porthole, which lets
chloride into cells, is also critical in digestion,
hearing, balance and fertility.
The researchers suggest that digestive system cells
and odor-detecting cells use the same chloride porthole, or
ion transporter — the former to facilitate secretion
of digestive juices, and the latter to communicate
information about scents to the brain.
Although scientists have long known that odor-sensing
cells require lots of charged chloride atoms, or ions, to
relay odor signals to the brain, they did not know how
cells keep levels of chloride high inside the cells. Now,
Johns Hopkins researchers have shown that these high
chloride levels in odor-detecting cells depend on the same
transporter, known as NKCC1, used in many other types of
cells as well.
"It's not unusual for the body to use the same
machinery to solve different problems," said one of the
lead authors, Jonathan Bradley, a postdoctoral fellow in
neuroscience. "Chloride is a kind of jack-of-all-trades
that cells can hijack to do what they want."
Odor-detecting nerve cells are long and thin,
extending from the tissues lining the nose where odors are
sensed all the way to the brain. When you smell cookies
baking, odor molecules bind to these cells, triggering a
series of molecular "gates" on the cell surface to open.
The open gates let charged ions, including chloride, move
in and out of the cell, creating differences in charge
between the inside and outside of the cell. Such
differences allow electrical signals to travel to the
brain, telling you that homemade cookies are nearby.
Bradley and co-author Johannes Reisert suspected NKCC1
might be involved in this process precisely because of the
transporter's known importance in regulating chloride in
many other tissues. Since NKCC1 appears in other cell
types, and because odor-detecting nerve cell neurons need
large amounts of chloride to sense odors, Reisert and
Bradley hypothesized that NKCC1 was responsible for
maintaining high chloride levels in odor-sensing cells
To test their idea, the researchers exposed individual
odor-detecting nerve cells from mice to odor molecules.
Unlike normal cells, those without functional NKCC1 had no
detectable chloride movement, indicating that the NKCC1
transporter was indeed responsible for the necessary
Bradley and Reisert also discovered that the porthole
was located on an unexpected region of the odor-detecting
cell. However, its location on these cells corresponds to
its location on cells that line the digestive tract,
reinforcing the idea of "borrowed" machinery.
"At first we were surprised to find this location of
the transporter," Bradley said, "but in hindsight it makes
sense — both types of cells need to keep chloride high in
order to do their jobs, and the transporter's location
Now that the chloride-controlling machinery in the
nose is known, scientists can probe details of chloride's
involvement in sending information to the brain, the
researchers say. Bradley and Reisert suspect that having
lots of chloride available in odor-detecting cells may help
the brain discriminate between different smells.
"The involvement of chloride might also make the
cells' response to odor more robust and reliable," said
Reisert, also a postdoctoral fellow in neuroscience.
The researchers plan to study the behavior of mice
without NKCC1 and are now attempting to clone and
characterize the chloride transporter to get a better sense
of how chloride is required for odor detection.
These studies were funded by the Howard Hughes Medical
Institute. The authors on the paper were Reisert, Jun Lai,
King-Wai Yau and Bradley, all from Johns Hopkins.