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February 24, 2005
CELLULAR PORTHOLE CONNECTS ODORS TO BRAIN
Porthole used in both odor-detecting cells and digestion-aiding cells
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 of the cells. Now 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," notes one of the lead authors, Jonathan Bradley, Ph.D., 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 home-made cookies are nearby.
Bradley and co-author Johannes Reisert, Ph.D., 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 cells 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 too.
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 chloride current.
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," says Bradley, "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 helps them."
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," says 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.
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